Catheter device and method for inducing negative pressure in a patient&#39;s bladder

ABSTRACT

A catheter includes an elongated tube having a distal portion having a distal end and a sidewall defining at least one drainage lumen. The sidewall includes a drainage portion which allows fluid to pass through the sidewall and into the drainage lumen. The catheter also includes a permeable tissue support. The tissue support is configured to be deployed in the urinary tract to maintain the distal end of the elongated tube at a predetermined position in a bladder, a ureter, a renal pelvis, or a kidney of the patient. When deployed, the permeable tissue support defines a three-dimensional shape of sufficient size to permit flow of at least a portion of fluid from the urinary tract through the tissue support and drainage portion of the elongated tube to the at least one drainage lumen.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 15/687,064 filed Aug. 25, 2017, which is a continuation-in-partof U.S. patent application Ser. No. 15/411,884 filed Jan. 20, 2017,which is a continuation-in-part of U.S. patent application Ser. No.15/214,955 filed Jul. 20, 2016, which claims the benefit of U.S.Provisional Application No. 62/300,025 filed Feb. 25, 2016, U.S.Provisional Application No. 62/278,721, filed Jan. 14, 2016, U.S.Provisional Application No. 62/260,966 filed Nov. 30, 2015, and U.S.Provisional Application No. 62/194,585, filed Jul. 20, 2015, each ofwhich is incorporated by reference herein in its entirety.

Also, this application is a continuation-in-part of U.S. patentapplication Ser. No. 15/687,083 filed Aug. 25, 2017, which is acontinuation-in-part of U.S. patent application Ser. No. 15/411,884filed Jan. 20, 2017, which is a continuation-in-part of U.S. patentapplication Ser. No. 15/214,955 filed Jul. 20, 2016, which claims thebenefit of U.S. Provisional Application No. 62/300,025 filed Feb. 25,2016, U.S. Provisional Application No. 62/278,721, filed Jan. 14, 2016,U.S. Provisional Application No. 62/260,966 filed Nov. 30, 2015, andU.S. Provisional Application No. 62/194,585, filed Jul. 20, 2015, eachof which is incorporated by reference herein in its entirety.

Also, this application is a continuation-in-part of U.S. patentapplication Ser. No. 15/745,823 filed Jan. 18, 2018, which is the U.S.national phase of PCT/US2016/043101, filed Jul. 20, 2016, which claimsthe benefit of U.S. Provisional Application No. 62/300,025 filed Feb.25, 2016, U.S. Provisional Application No. 62/278,721, filed Jan. 14,2016, U.S. Provisional Application No. 62/260,966 filed Nov. 30, 2015,and U.S. Provisional Application No. 62/194,585, filed Jul. 20, 2015,each of which is incorporated by reference herein in its entirety.

Also, this application claims the benefit of U.S. ProvisionalApplication No. 62/489,789 filed Apr. 25, 2017 and U.S. ProvisionalApplication No. 62/489,831 filed Apr. 25, 2017.

BACKGROUND Technical Field

The present disclosure relates to devices and methods for treatingimpaired renal function across a variety of disease states and, inparticular, to devices and methods for collection of urine andinducement of negative and/or positive pressure in portions of apatient's urinary tract.

BACKGROUND

The renal or urinary system includes a pair of kidneys, each kidneybeing connected by a ureter to the bladder, and a urethra for drainingurine produced by the kidneys from the bladder. The kidneys performseveral vital functions for the human body including, for example,filtering the blood to eliminate waste in the form of urine. The kidneysalso regulate electrolytes (e.g., sodium, potassium and calcium) andmetabolites, blood volume, blood pressure, blood pH, fluid volume,production of red blood cells, and bone metabolism. Adequateunderstanding of the anatomy and physiology of the kidneys is useful forunderstanding the impact that altered hemodynamics other fluid overloadconditions have on their function.

In normal anatomy, the two kidneys are located retroperitoneally in theabdominal cavity. The kidneys are bean-shaped encapsulated organs. Urineis formed by nephrons, the functional unit of the kidney, and then flowsthrough a system of converging tubules called collecting ducts. Thecollecting ducts join together to form minor calyces, then majorcalyces, which ultimately join near the concave portion of the kidney(renal pelvis). A major function of the renal pelvis is to direct urineflow to the ureter. Urine flows from the renal pelvis into the ureter, atube-like structure that carries the urine from the kidneys into thebladder. The outer layer of the kidney is called the cortex, and is arigid fibrous encapsulation. The interior of the kidney is called themedulla. The medulla structures are arranged in pyramids.

Each kidney is made up of approximately one million nephrons. Aschematic drawing of a nephron 1102 is shown in FIG. 39. Each nephronincludes the glomerulus 1110, Bowman's capsule 1112, and tubules 1114.The tubules 1114 include the proximal convoluted tubule 1116, the loopof Henle 1118, the distal convoluted tubule 1120, and the collectingduct 1122. The nephrons 1102 contained in the cortex layer of the kidneyare distinct from the anatomy of those contained in the medulla. Theprincipal difference is the length of the loop of Henle 1118. Medullarynephrons contain a longer loop of Henle, which, under normalcircumstances, allows greater regulation of water and sodiumreabsorption than in the cortex nephrons.

The glomerulus is the beginning of the nephron, and is responsible forthe initial filtration of blood. Afferent arterioles pass blood into theglomerular capillaries, where hydrostatic pressure pushes water andsolutes into Bowman's capsule. Net filtration pressure is expressed asthe hydrostatic pressure in the afferent arteriole minus the hydrostaticpressure in Bowman's space minus the osmotic pressure in the efferentarteriole.Net Filtration Pressure=Hydrostatic Pressure(AfferentArteriole)−Hydrostatic Pressure(Bowman's Space)−OsmoticPressure(Efferent Arteriole)  (Equation 1)

The magnitude of this net filtration pressure defined by Equation 1determines how much ultra-filtrate is formed in Bowman's space anddelivered to the tubules. The remaining blood exits the glomerulus viathe efferent arteriole. Normal glomerular filtration, or delivery ofultra-filtrate into the tubules, is about 90 ml/min/1.73 m².

The glomerulus has a three-layer filtration structure, which includesthe vascular endothelium, a glomerular basement membrane, and podocytes.Normally, large proteins such as albumin and red blood cells, are notfiltered into Bowman's space. However, elevated glomerular pressures andmesangial expansion create surface area changes on the basement membraneand larger fenestrations between the podocytes allowing larger proteinsto pass into Bowman's space.

Ultra-filtrate collected in Bowman's space is delivered first to theproximal convoluted tubule. Re-absorption and secretion of water andsolutes in the tubules is performed by a mix of active transportchannels and passive pressure gradients. The proximal convoluted tubulesnormally reabsorb a majority of the sodium chloride and water, andnearly all glucose and amino acids that were filtered by the glomerulus.The loop of Henle has two components that are designed to concentratewastes in the urine. The descending limb is highly water permeable andreabsorbs most of the remaining water. The ascending limb reabsorbs 25%of the remaining sodium chloride, creating a concentrated urine, forexample, in terms of urea and creatinine. The distal convoluted tubulenormally reabsorbs a small proportion of sodium chloride, and theosmotic gradient creates conditions for the water to follow.

Under normal conditions, there is a net filtration of approximately 14mmHg. The impact of venous congestion can be a significant decrease innet filtration, down to approximately 4 mmHg. See Jessup M., Thecardiorenal syndrome: Do we need a change of strategy or a change oftactics?, JACC 53(7):597-600, 2009 (hereinafter “Jessup”). The secondfiltration stage occurs at the proximal tubules. Most of the secretionand absorption from urine occurs in tubules in the medullary nephrons.Active transport of sodium from the tubule into the interstitial spaceinitiates this process. However, the hydrostatic forces dominate the netexchange of solutes and water. Under normal circumstances, it isbelieved that 75% of the sodium is reabsorbed back into lymphatic orvenous circulation. However, because the kidney is encapsulated, it issensitive to changes in hydrostatic pressures from both venous andlymphatic congestion. During venous congestion the retention of sodiumand water can exceed 85%, further perpetuating the renal congestion. SeeVerbrugge et al., The kidney in congestive heart failure: Arenatriuresis, sodium, and diruetucs really the good, the bad and theugly? European Journal of Heart Failure 2014:16, 133-42 (hereinafter“Verbrugge”).

Venous congestion can lead to a prerenal form of acute kidney injury(AKI). Prerenal AKI is due to a loss of perfusion (or loss of bloodflow) through the kidney. Many clinicians focus on the lack of flow intothe kidney due to shock. However, there is also evidence that a lack ofblood flow out of the organ due to venous congestion can be a clinicallyimportant sustaining injury. See Damman K, Importance of venouscongestion for worsening renal function in advanced decompensated heartfailure, JACC 17:589-96, 2009 (hereinafter “Damman”).

Prerenal AKI occurs across a wide variety of diagnoses requiringcritical care admissions. The most prominent admissions are for sepsisand Acute Decompensated Heart Failure (ADHF). Additional admissionsinclude cardiovascular surgery, general surgery, cirrhosis, trauma,burns, and pancreatitis. While there is wide clinical variability in thepresentation of these disease states, a common denominator is anelevated central venous pressure. In the case of ADHF, the elevatedcentral venous pressure caused by heart failure leads to pulmonaryedema, and, subsequently, dyspnea in turn precipitating the admission.In the case of sepsis, the elevated central venous pressure is largely aresult of aggressive fluid resuscitation. Whether the primary insult waslow perfusion due to hypovolemia or sodium and fluid retention, thesustaining injury is the venous congestion resulting in inadequateperfusion.

Hypertension is another widely recognized state that createsperturbations within the active and passive transport systems of thekidney(s). Hypertension directly impacts afferent arteriole pressure andresults in a proportional increase in net filtration pressure within theglomerulus. The increased filtration fraction also elevates theperitubular capillary pressure, which stimulates sodium and waterre-absorption. See Verbrugge.

Because the kidney is an encapsulated organ, it is sensitive to pressurechanges in the medullary pyramids. The elevated renal venous pressurecreates congestion that leads to a rise in the interstitial pressures.The elevated interstitial pressures exert forces upon both theglomerulus and tubules. See Verburgge. In the glomerulus, the elevatedinterstitial pressures directly oppose filtration. The increasedpressures increase the interstitial fluid, thereby increasing thehydrostatic pressures in the interstitial fluid and peritubularcapillaries in the medulla of the kidney. In both instances, hypoxia canensue leading to cellular injury and further loss of perfusion. The netresult is a further exacerbation of the sodium and water re-absorptioncreating a negative feedback. See Verbrugge, 133-42. Fluid overload,particularly in the abdominal cavity is associated with many diseasesand conditions, including elevated intra-abdominal pressure, abdominalcompartment syndrome, and acute renal failure. Fluid overload can beaddressed through renal replacement therapy. See Peters, C. D., Shortand Long-Term Effects of the Angiotensin II Receptor BlockerIrbesartanon Intradialytic Central Hemodynamics: A RandomizedDouble-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIRStudy), PLoS ONE (2015) 10(6): e0126882.doi:10.1371/journal.pone.0126882 (hereinafter “Peters”). However, such aclinical strategy provides no improvement in renal function for patientswith the cardiorenal syndrome. See Bart B, Ultrafiltration indecompensated heart failure with cardiorenal syndrome, NEJM 2012;367:2296-2304 (hereinafter “Bart”).

In view of such problematic effects of fluid retention, devices andmethods for improving removal of urine from the urinary tract and,specifically for increasing quantity and quality of urine output fromthe kidneys, are needed.

SUMMARY

According to an aspect of the disclosure, a fluid collection catheterconfigured to be deployed in a urinary tract of a patient includes: anelongated tube having a proximal portion configured for placement in aurethra of the patient, a distal portion comprising a distal end, and asidewall extending between a proximal end and the distal end of theelongated tube defining at least one drainage lumen extending throughthe tube, the sidewall comprising a drainage portion which allows fluidto pass through the sidewall and into the drainage lumen. The catheteralso includes a permeable tissue support directly or indirectlyconnected to the distal portion of the elongated tube and extendingaxially and/or radially therefrom, the tissue support being configuredto be deployed in the urinary tract to maintain the distal end of theelongated tube at a predetermined position in a bladder, a ureter, arenal pelvis, or a kidney of the patient. When deployed, the permeabletissue support defines a three-dimensional shape of sufficient size topermit flow of at least a portion of fluid from the urinary tractthrough the tissue support and drainage portion of the elongated tube tothe at least one drainage lumen.

According to another aspect of the disclosure, a method of inducing anegative pressure to a urinary tract of a patient for enhancing urineexcretion therefrom includes: inserting a distal portion of an elongatedtube of a urine collection catheter into the urinary tract, theelongated tube comprising a proximal portion configured for placement ina urethra of the patient, a distal portion comprising a distal end, anda sidewall extending between a proximal end and the distal end of theelongated tube defining at least one drainage lumen extending throughthe tube, the sidewall comprising a drainage portion which allows fluidto pass through the sidewall and into the drainage lumen. The methodalso includes a step of deploying a permeable tissue support directly orindirectly connected to and extending axially and/or radially from theelongated tube at a predetermined position in a bladder, a ureter, arenal pelvis, or a kidney of the patient, wherein the permeable tissuesupport is configured to be deployed in the urinary tract to maintainthe distal end of the elongated tube at the predetermined position, andwherein, when deployed, the permeable tissue support defines athree-dimensional shape of sufficient size to permit flow of at least aportion of fluid from the urinary tract through the permeable tissuesupport and drainage portion of the sidewall to the at least onedrainage lumen extending through the elongated tube. The method alsoincludes a step of inducing a negative pressure through the at least onedrainage lumen of the elongated tube to draw urine from the urinarytract into the drainage lumen.

According to another aspect of the disclosure, a system for drawingurine from a urinary tract of a patient includes an elongated tubecomprising a proximal portion configured for placement in a urethra ofthe patient, a distal portion comprising a distal end, and a sidewallextending between a proximal end and the distal end of the elongatedtube defining at least one drainage lumen extending through the tube,the sidewall comprising a drainage portion which allows fluid to passthrough the sidewall and into the drainage lumen. The system alsoincludes a permeable tissue support directly or indirectly connected tothe distal portion of the elongated tube and extending axially and/orradially therefrom, the tissue support being configured to be deployedin the urinary tract to maintain the distal end of the elongated tube ata predetermined position in a bladder, a ureter, a renal pelvis, or akidney of the patient. When deployed, the permeable tissue supportdefines a three-dimensional shape of sufficient size to permit flow ofat least a portion of fluid from the urinary tract through the permeabletissue support and drainage portion of the sidewall to the at least onedrainage lumen extending through the elongated tube. The system alsoincludes a pump in fluid connection with the drainage lumen of theelongated tube, wherein the pump is configured to introduce an internalnegative pressure through the drainage lumen to the urinary tract of thepatient to draw urine from the urinary tract.

Non-limiting examples of the present invention will now be described inthe following numbered clauses:

Clause 1: A fluid collection catheter configured to be deployed in aurinary tract of a patient, comprising: an elongated tube comprising aproximal portion configured for placement in a urethra of the patient, adistal portion comprising a distal end, and a sidewall extending betweena proximal end and the distal end of the elongated tube defining atleast one drainage lumen extending through the tube, the sidewallcomprising a drainage portion which allows fluid to pass through thesidewall and into the drainage lumen; and a permeable tissue supportdirectly or indirectly connected to the distal portion of the elongatedtube and extending axially and/or radially therefrom, the tissue supportbeing configured to be deployed in the urinary tract to maintain thedistal end of the elongated tube at a predetermined position in abladder, a ureter, a renal pelvis, or a kidney of the patient, wherein,when deployed, the permeable tissue support defines a three-dimensionalshape of sufficient size to permit flow of at least a portion of fluidfrom the urinary tract through the tissue support and drainage portionof the elongated tube to the at least one drainage lumen.

Clause 2: The catheter of clause 1, wherein, when deployed, thepermeable tissue support at least partially encloses the drainageportion of the sidewall.

Clause 3: The catheter of clause 1 or clause 2, wherein the permeabletissue support comprises a permeable material.

Clause 4: The catheter of clause 3, wherein the permeable materialcomprises at least one of biocompatible polymer fiber(s); metallicfiber(s), porous film(s), film(s) comprising one or more apertures,fabric(s), or any combination thereof.

Clause 5: The catheter of clause 3 or clause 4, wherein the permeablematerial has a thickness of from about 0.5 mm to about 5 mm.

Clause 6: The catheter of any of clauses 1 to 5, wherein the permeabletissue support comprises a plurality of elongated members having a firstend and/or a second end connected to the elongated tube woven togetherto form a mesh of elongated members.

Clause 7: The catheter of any of clauses 1 to 6, wherein, when deployedin the patient's bladder, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of thebladder is exposed to an internal negative pressure.

Clause 8: The catheter of any of clauses 1 to 7, wherein, when deployedin the patient's bladder, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of thebladder is exposed to an internal negative pressure of from 5 to 150mmHg.

Clause 9: The catheter of any of clauses 1 to 8, wherein, when deployedin the patient's bladder, the permeable tissue support is configured toinhibit mucosal tissue from occluding at least a portion of the drainageportion of the sidewall.

Clause 10: The catheter of any of clauses 1 to 9, wherein the permeabletissue support has a maximum outer diameter of from about 10 mm to about100 mm.

Clause 11: The catheter of any of clauses 1 to 10, wherein a lengthbetween a proximal end and a distal end of the permeable tissue supportis from about 10 mm to about 100 mm.

Clause 12: The catheter of any of clauses 1 to 11, wherein the elongatedtube has an outer diameter of from about 0.5 mm to about 10 mm.

Clause 13: The catheter of any of clauses 1 to 12, wherein the elongatedtube has an inner diameter of from about 0.5 mm to about 9 mm.

Clause 14: The catheter of any of clauses 1 to 13, wherein, whendeployed, the three dimensional shape has a volume of from 0.1 cm³ to500 cm³.

Clause 15: The catheter of any of clauses 1 to 14, wherein, whendeployed, a middle portion of the permeable tissue support bulgesradially outward from proximal and distal ends of the permeable tissuesupport, such that an outer diameter of the permeable tissue supportincreases from the proximal end to the middle portion thereof anddecreases from the middle portion to the distal end thereof.

Clause 16: The catheter of any of clauses 1 to 14, wherein, whendeployed, the permeable tissue support comprises at least one middleportion located between a proximal portion and a distal portion of thetissue support, and wherein the middle portion has a minimum outerdiameter which is less than a maximum outer diameter of the proximalportion and the distal portion of the permeable tissue support.

Clause 17: The catheter of clause 16, wherein the minimum outer diameterof the middle portion is from about 2.5 mm to about 20 mm less than themaximum outer diameter of the proximal portion or the distal portion ofthe tissue support.

Clause 18: The catheter of clause 16 or clause 17, wherein the minimumouter diameter of the middle portion is from equal to an outer diameterof the elongated to about 40 mm greater than an outer diameter of theelongated tube.

Clause 19: The catheter of any of clauses 16 to 18, wherein the minimumouter diameter of the middle portion is from about 10% to about 99% lessthan the maximum outer diameter of the proximal portion or the distalportion of the tissue support.

Clause 20: The catheter of any of clauses 1 to 19, wherein the drainageportion of the sidewall comprises a perforated section of tubingcomprising at least one perforation permitting fluid to flow through thesidewall of the elongated tube into the at least one drainage lumen.

Clause 21: The catheter of clause 20, wherein the at least oneperforation has one or more shapes, each shape being selected from atleast one of a circular shape, an elliptical shape, a square shape, aregular polygonal shape, an irregular circular shape, or an irregularpolygonal shape, or combinations thereof.

Clause 22: The catheter of clause 20 or clause 21, wherein the at leastone perforation has a diameter of about 0.05 mm to about 2.0 mm.

Clause 23: The catheter of any of clauses 20 to 22, wherein, whendeployed in the patient's bladder, the permeable tissue support isconfigured to inhibit any portion of a wall of the bladder fromoccluding the at least one perforation of the drainage portion upondelivery of negative pressure to an interior of the bladder through thedrainage lumen of the elongated tube.

Clause 24: The catheter of any of clauses 1 to 23, wherein, whendeployed in the patient's bladder, the permeable tissue support isconfigured to inhibit any portions of the bladder wall from occluding orobstructing ureteral orifices upon delivery of negative pressure to thebladder through the drainage lumen of the tube.

Clause 25: The catheter of any of clauses 1 to 24, further comprising atleast one collar slidably connected to the elongated tube, wherein atleast a portion of the permeable tissue support is connected to thecollar.

Clause 26: The catheter of clause 25, wherein sliding the collar alongthe elongated tube deploys or retracts the permeable tissue support.

Clause 27: The catheter of any of clauses 1 to 24, wherein the elongatedtube comprises an inner tube, further comprising an elongated outer tubeat least partially surrounding the inner tube, the outer tube having aproximal end portion, a distal end portion, and a sidewall extendingtherebetween, wherein a distal portion of the permeable tissue supportis connected to the inner tube and a proximal portion of the permeabletissue support is connected to the outer elongated tube.

Clause 28: The catheter of clause 27, wherein sliding the inner tuberelative to the outer tube causes at least one of deployment andretraction of the permeable tissue support.

Clause 29: The catheter of clause 27 or clause 28, wherein the drainageportion of the sidewall comprises one or more perforations, and whereinat least one perforations is at least partially enclosed by thepermeable tissue support, when the permeable tissue support is deployed.

Clause 30: The catheter of any of clauses 1 to 29, further comprising adelivery catheter comprising a proximal end configured to remainexternal to the body, a distal end for insertion into the bladder, asidewall extending therebetween, and at least one lumen sized to receivethe elongated tube and permeable tissue support, wherein the deliverycatheter is configured to maintain the permeable tissue support in aretracted position during insertion of the permeable tissue support tothe urinary tract of the patient.

Clause 31: The catheter of clause 30, wherein the delivery catheter hasan inner diameter of from about 5 mm to about 20 mm.

Clause 32: The catheter of clause 30 or clause 31, wherein the permeabletissue support is biased to a deployed position, such that when pushedfrom the distal end of the delivery sheath, the permeable tissue supportadopts its deployed configuration.

Clause 33: The catheter of any of clauses 1 to 32, wherein the permeabletissue support is configured to transition from a retracted position inwhich at least a portion of an inner surface of the tissue supportcontacts an outer surface of the sidewall to a deployed position inwhich the portion of the inner surface of the tissue support is spacedapart from the sidewall.

Clause 34: A method of inducing a negative pressure to a urinary tractof a patient for enhancing urine excretion therefrom, the methodcomprising: inserting a distal portion of an elongated tube of a urinecollection catheter into the urinary tract, the elongated tubecomprising a proximal portion configured for placement in a urethra ofthe patient, a distal portion comprising a distal end, and a sidewallextending between a proximal end and the distal end of the elongatedtube defining at least one drainage lumen extending through the tube,the sidewall comprising a drainage portion which allows fluid to passthrough the sidewall and into the drainage lumen; deploying a permeabletissue support directly or indirectly connected to and extending axiallyand/or radially from the elongated tube at a predetermined position in abladder, a ureter, a renal pelvis, or a kidney of the patient, whereinthe permeable tissue support is configured to be deployed in the urinarytract to maintain the distal end of the elongated tube at thepredetermined position, and wherein, when deployed, the permeable tissuesupport defines a three-dimensional shape of sufficient size to permitflow of at least a portion of fluid from the urinary tract through thepermeable tissue support and drainage portion of the sidewall to the atleast one drainage lumen extending through the elongated tube; andinducing a negative pressure through the at least one drainage lumen ofthe elongated tube to draw urine from the urinary tract into thedrainage lumen.

Clause 35: The method of clause 34, wherein, when deployed, thepermeable tissue support at least partially encloses the drainageportion of the sidewall.

Clause 36: The method of clause 34 or clause 35, wherein the permeabletissue support comprises a permeable material.

Clause 37: The method of clause 36, wherein the permeable materialcomprises at least one of biocompatible polymer fiber(s); metallicfiber(s), porous film(s), film(s) comprising one or more apertures,fabric(s), or any combination thereof.

Clause 38: The method of any of clauses 34 to 37, wherein, when deployedin the patient's bladder, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of thebladder is exposed to an internal negative pressure.

Clause 39: The method of any of clauses 34 to 38, wherein, when deployedin the patient's bladder, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of thebladder is exposed to an internal negative pressure of from about 5 mmHgto about 125 mmHg.

Clause 40: The method of any of clauses 34 to 39, wherein inducing thenegative pressure in the drainage lumen comprises coupling a mechanicalpump in fluid communication with the proximal end of the drainage lumento draw urine from the bladder into the drainage lumen through thedrainage portion of the sidewall.

Clause 41: The method of any of clauses 34 to 40, wherein inducingnegative pressure comprises applying a negative pressure of from about0.1 mmHg to about 150 mmHg to the proximal end of the elongated tube.

Clause 42: The method of any of clauses 34 to 41, wherein the elongatedtube is inserted into the bladder in a delivery catheter, and whereindeploying the permeable tissue support comprises retracting the deliverycatheter to expose the permeable tissue support.

Clause 43: The method of clause 42, wherein the permeable tissue supportadopts a deployed position when the delivery catheter is retracted.

Clause 44: A system for drawing urine from a urinary tract of a patient,the system comprising: a urine collection catheter comprising: anelongated tube comprising a proximal portion configured for placement ina urethra of the patient, a distal portion comprising a distal end, anda sidewall extending between a proximal end and the distal end of theelongated tube defining at least one drainage lumen extending throughthe tube, the sidewall comprising a drainage portion which allows fluidto pass through the sidewall and into the drainage lumen; and apermeable tissue support directly or indirectly connected to the distalportion of the elongated tube and extending axially and/or radiallytherefrom, the tissue support being configured to be deployed in theurinary tract to maintain the distal end of the elongated tube at apredetermined position in a bladder, a ureter, a renal pelvis, or akidney of the patient, wherein, when deployed, the permeable tissuesupport defines a three-dimensional shape of sufficient size to permitflow of at least a portion of fluid from the urinary tract through thepermeable tissue support and drainage portion of the sidewall to the atleast one drainage lumen extending through the elongated tube; and apump in fluid connection with the drainage lumen of the elongated tube,wherein the pump is configured to introduce an internal negativepressure through the drainage lumen to the urinary tract of the patientto draw urine from the urinary tract.

Clause 45: The system of clause 44, wherein the permeable tissue supportat least partially encloses the open distal end of the elongated tube.

Clause 46: The system of clause 44 or clause 45, wherein the permeabletissue support comprises a permeable material comprising at least one ofbiocompatible polymer fiber(s); metallic fiber(s), porous film(s),film(s) comprising one or more apertures, fabric(s), or any combinationthereof.

Clause 47: The system of any of clauses 44 to 46, wherein, when deployedin the patient's bladder, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of thebladder is exposed to an internal negative pressure.

Clause 48: The system of any of clauses 44 to 47, wherein, when deployedin the patient's bladder, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of thebladder is exposed to an internal negative pressure of from about 5 mmHgto about 150 mmHg.

Clause 49: The system of any of clauses 44 to 48, wherein, when deployedin the patient's bladder, the permeable tissue support is configured toinhibit mucosal tissue from occluding at least a portion of the drainageportion of the sidewall.

Clause 50: The system of any of clauses 44 to 49, wherein the pumpprovides a sensitivity of about 10 mmHg or less.

Clause 51: The system of any of clauses 44 to 50, wherein the pump isconfigured to provide a negative pressure of from about 0.1 mmHg toabout 150 mmHg.

Clause 52: The system of any of clauses 44 to 51, wherein the pump isconfigured to provide intermittent negative pressure.

Clause 53: The system of any of clauses 44 to 52, wherein the pump isconfigured to alternate between providing negative pressure andproviding positive pressure.

Clause 54: The system of any of clauses 44 to 53, wherein the pump isconfigured to alternate between providing negative pressure andequalizing pressure to atmosphere.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and characteristics of the present disclosure,as well as the methods of operation and functions of the relatedelements of structures and the combination of parts and economies ofmanufacture, will become more apparent upon consideration of thefollowing description and the appended claims with reference to theaccompanying drawings, all of which form a part of this specification,wherein like reference numerals designate corresponding parts in thevarious figures. It is to be expressly understood, however, that thedrawings are for the purpose of illustration and description only andare not intended as a definition of the limit of the invention.

Further features and other examples and advantages will become apparentfrom the following detailed description made with reference to thedrawings in which:

FIG. 1 is a schematic drawing of a urine collection catheter deployedwithin the bladder of a male patient according to an example of thedisclosure;

FIG. 2 is another schematic drawing of the urine collection catheterdeployed within a patient's bladder according to an example of thedisclosure;

FIG. 3 is a schematic drawing of a urine collection system including aurine collection catheter deployed in a bladder of a patient and a fluidpump for providing negative pressure to the urinary tract according toexample of the disclosure;

FIG. 4A is a side view of a urine collection catheter according to anexample of the present disclosure;

FIG. 4B is a cross-section view of the urine collection catheter of FIG.4A;

FIG. 5A is a side view of the urine collection catheter of FIG. 4A in adeployed position and including a delivery catheter according to anexample of the disclosure;

FIG. 5B is a side view of the urine collection catheter of FIG. 4Aretracted within the delivery catheter of FIG. 5A according to anexample of the disclosure;

FIG. 6A is a side view of another urine collection catheter according toan example of the present disclosure;

FIG. 6B is a cross-section view of the urine collection catheter of FIG.6A;

FIG. 7A is a side view of another urine collection catheter according toan example of the present disclosure;

FIG. 7B is a cross-section view of the urine collection catheter of FIG.7A;

FIG. 8 is a schematic drawing of a urine collection system including aurine collection catheter deployed in a bladder and ureteral stentsaccording to an example of the present disclosure;

FIG. 9 is a schematic drawing of an exemplary ureteral stent as is knownin the prior art;

FIG. 10A is a schematic drawing of a urine collection system including aurine collection catheter deployed in the bladder and ureteral stentsincluding a helical retention portion according to an example of thepresent disclosure;

FIG. 10B is a schematic drawing of the helical retention portion of theureteral stent of FIG. 10A;

FIG. 10C is a schematic drawing of another embodiment of a helicalretention portion of a ureteral stent according to an example of thepresent disclosure;

FIG. 11 is a schematic drawing of a urine collection system includingurine collection catheters deployed in the renal pelvis or kidney of apatient according to an example of the present disclosure;

FIG. 12A is a flow chart illustrating a process for insertion anddeployment of a ureteral catheter or urine collection assembly accordingto an example of the present disclosure;

FIG. 12B is a flow chart illustrating a process for applying negativepressure using a ureteral catheter or urine collection assemblyaccording to an example of the present disclosure;

FIG. 13 is a schematic drawing of a system for inducing negativepressure to the urinary tract of a patient according to an example ofthe present disclosure;

FIG. 14A is a plan view of a pump for use with the system of FIG. 13according to an example of the present disclosure;

FIG. 14B is a side elevation view of the pump of FIG. 14A;

FIG. 15 is a flow chart illustrating a process for reducing creatinineand/or protein levels of a patient according to an example of thedisclosure;

FIG. 16 is a flow chart illustrating a process for treating a patientundergoing fluid resuscitation according to an example of thedisclosure;

FIG. 17 is a schematic drawing of an experimental set-up for evaluatingnegative pressure therapy in a swine model;

FIG. 18 is a graph of creatinine clearance rates for tests conductedusing the experimental set-up shown in FIG. 17;

FIG. 19A is a low magnification photomicrograph of kidney tissue from acongested kidney treated with negative pressure therapy;

FIG. 19B is a high magnification photomicrograph of the kidney tissueshown in FIG. 19A;

FIG. 19C is a low magnification photomicrograph of kidney tissue from acongested and untreated (e.g., control) kidney;

FIG. 19D is a high magnification photomicrograph of the kidney tissueshown in FIG. 19C; and

FIG. 20 is a graph of serum albumin relative to baseline for testsconduct on swine using the experimental method described herein.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, the singular form of “a”, “an”, and “the” include pluralreferents unless the context clearly states otherwise.

As used herein, the terms “right”, “left”, “top”, and derivativesthereof shall relate to the invention as it is oriented in the drawingfigures. The term “proximal” refers to the portion of the catheterdevice that is manipulated or contacted by a user and/or to a portion ofan indwelling catheter nearest to the urinary tract access site. Theterm “distal” refers to the opposite end of the catheter device that isconfigured to be inserted into a patient and/or to the portion of thedevice that is inserted farthest into the patient's urinary tract.However, it is to be understood that the invention can assume variousalternative orientations and, accordingly, such terms are not to beconsidered as limiting. Also, it is to be understood that the inventioncan assume various alternative variations and stage sequences, exceptwhere expressly specified to the contrary. It is also to be understoodthat the specific devices and processes illustrated in the attacheddrawings, and described in the following specification, are examples.Hence, specific dimensions and other physical characteristics related tothe embodiments disclosed herein are not to be considered as limiting.

For the purposes of this specification, unless otherwise indicated, allnumbers expressing quantities of ingredients, reaction conditions,dimensions, physical characteristics, and so forth used in thespecification and claims are to be understood as being modified in allinstances by the term “about.” Unless indicated to the contrary, thenumerical parameters set forth in the following specification andattached claims are approximations that can vary depending upon thedesired properties sought to be obtained by the present invention.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements.

Also, it should be understood that any numerical range recited herein isintended to include all sub-ranges subsumed therein. For example, arange of “1 to 10” is intended to include any and all sub-ranges betweenand including the recited minimum value of 1 and the recited maximumvalue of 10, that is, all sub-ranges beginning with a minimum valueequal to or greater than 1 and ending with a maximum value equal to orless than 10, and all sub-ranges in between, e.g., 1 to 6.3, or 5.5 to10, or 2.7 to 6.1.

As used herein, the terms “communication” and “communicate” refer to thereceipt or transfer of one or more signals, messages, commands, or othertype of data. For one unit or component to be in communication withanother unit or component means that the one unit or component is ableto directly or indirectly receive data from and/or transmit data to theother unit or component. This can refer to a direct or indirectconnection that can be wired and/or wireless in nature. Additionally,two units or components can be in communication with each other eventhough the data transmitted can be modified, processed, routed, and thelike, between the first and second unit or component. For example, afirst unit can be in communication with a second unit even though thefirst unit passively receives data, and does not actively transmit datato the second unit. As another example, a first unit can be incommunication with a second unit if an intermediary unit processes datafrom one unit and transmits processed data to the second unit. It willbe appreciated that numerous other arrangements are possible.

Fluid retention and venous congestion are central problems in theprogression to advanced renal disease. Excess sodium ingestion coupledwith relative decreases in excretion leads to isotonic volume expansionand secondary compartment involvement. In some examples, the presentinvention is generally directed to devices and methods for facilitatingdrainage of urine or waste from the bladder, ureter, and/or kidney(s) ofa patient. In some examples, the present invention is generally directedto devices and methods for inducing a negative pressure in the bladder,ureter, and/or kidney(s) of a patient. While not intending to be boundby any theory, it is believed that applying a negative pressure to thebladder, ureter, and/or kidney(s) can offset the medullary nephrontubule re-absorption of sodium and water in some situations. Offsettingre-absorption of sodium and water can increase urine production,decrease total body sodium, and improve erythrocyte production. Sincethe intra-medullary pressures are driven by sodium and, therefore,volume overload, the targeted removal of excess sodium enablesmaintenance of volume loss. Removal of volume restores medullaryhemostasis. Normal urine production is 1.48-1.96 L/day (or 1-1.4ml/min).

Fluid retention and venous congestion are also central problems in theprogression of prerenal Acute Kidney Injury (AKI). Specifically, AKI canbe related to loss of perfusion or blood flow through the kidney(s).Accordingly, in some examples, the present invention facilitatesimproved renal hemodynamics and increases urine output for the purposeof relieving or reducing venous congestion. Further, it is anticipatedthat treatment and/or inhibition of AKI positively impacts and/orreduces the occurrence of other conditions, for example, reduction orinhibition of worsening renal function in patients with NYHA Class IIIand/or Class IV heart failure. Classification of different levels ofheart failure are described in The Criteria Committee of the New YorkHeart Association, (1994), Nomenclature and Criteria for Diagnosis ofDiseases of the Heart and Great Vessels, (9th ed.), Boston: Little,Brown & Co. pp. 253-256, the disclosure of which is incorporated byreference herein in its entirety. Reduction or inhibition of episodes ofAKI and/or chronically decreased perfusion may also be a treatment forStage 4 and/or Stage 5 chronic kidney disease. Chronic kidney diseaseprogression is described in National Kidney Foundation, K/DOQI ClinicalPractice Guidelines for Chronic Kidney Disease: Evaluation,Classification and Stratification. Am. J. Kidney Dis. 39:S1-S266, 2002(Suppl. 1), the disclosure of which is incorporated by reference hereinin its entirety.

With reference to FIGS. 1-3, an exemplary system 100 for inducingnegative pressure in a urinary tract of a patient for increasing renalperfusion is illustrated. It is noted, however, that the system 2described herein is but one example of a negative pressure system forinducing negative pressure that can be used with urine collectioncatheters 10 disclosed herein. The catheters 10 and other elementsdisclosed herein can also be used with other medical devices forcollecting fluid and/or providing negative pressure therapy within thescope of the present disclosure. In addition, in other examples, theurine collection catheters 10 disclosed herein can be connected to anunpressurized fluid collection container.

The system 2 comprises a urine collection catheter 10 deployed in theurinary tract and a pump 200 (shown in FIG. 3) for inducing the negativepressure in the urinary tract through the catheter 10. The patient'surinary tract comprises a patient's right kidney 112 and left kidney114. The kidneys 112, 114 are responsible for blood filtration andclearance of waste compounds from the body through urine. Urine producedby the right kidney 112 and the left kidney 114 is drained into apatient's bladder 110 through tubules, namely a right ureter 116 and aleft ureter 118, which are connected to the kidneys 112, 114 at a renalpelvis 120, 122. Urine may be conducted through the ureters 116, 118 byperistalsis of the ureter walls, as well as by gravity. The ureters 116,118 enter the bladder 110 through ureter orifices or openings 124, 126.As shown in FIGS. 1-3, the ureteral orifices or openings 124, 126 arepositioned at a midline of the bladder 110, approximately half waybetween an inferior bladder wall 100 a and a superior bladder wall 100 b(shown in FIG. 2). As such, proximal portions of the ureters 116, 118are shown in phantom in FIGS. 2 and 3 to indicate that such structurespass behind the bladder 110 and connect to the bladder 110 at theorifices or openings 124, 126.

The ureter orifices or openings 124, 126 are covered by soft tissuewhich essentially forms a one-way flap valve. When the bladder 110 iscollecting urine, the soft tissue is able to accommodate pressure fromthe peristalsis so that urine can pass from the ureters 116, 118 intothe bladder 110. When the bladder 110 contracts to expel urinetherefrom, the soft tissue is restrained against the ureter openings124, 126 to prevent backflow of urine from the bladder 110 back into theureters 116, 118. As described herein, in some examples, restraints,such as stents, catheters, tubes, and similar structures, can bepositioned to allow the ureter openings 124, 126 to remain open duringnegative pressure therapy so that the negative pressure can draw urineinto the bladder 110 and into catheter devices positioned in the bladder110.

The bladder 110 is a flexible and substantially hollow structure adaptedto collect urine until the urine is excreted from the body. The bladder110 is transitionable from an empty position (signified by referenceline E in FIGS. 2 and 3) to a full position (signified by reference lineF in FIGS. 2 and 3). Normally, when the bladder 110 reaches asubstantially full state, urine is permitted to drain from the bladder110 to a urethra 128 through a urethral sphincter or opening 130 locatedat a lower portion of the bladder 110. Contraction of the bladder 110can be responsive to stresses and pressure exerted on a trigone region132 (shown in FIG. 2) of the bladder 110, which is the triangular regionextending between the ureteral openings 124, 126 and the urethralopening 130. The trigone region 132 is sensitive to stress and pressure,such that as the bladder 110 begins to fill, pressure on the trigoneregion 132 increases. When a threshold pressure on the trigone region132 is exceeded, the ureteral sphincter or opening 130 relaxes andallows the bladder 110 to contract to expel collected urine through theurethra 128.

Urine Collection Catheters

The urine collection catheter 10 is shown deployed in the patient'sbladder 10 in FIGS. 1-3. Catheters configured to be deployed in otherportions of the urinary tract, such as the ureters 116, 118, renalpelvis 120, 122, or kidney(s) 112, 114, including similar supportstructures and deployment mechanisms to catheter 10 are describedelsewhere in the present application.

With continued reference to FIGS. 1-3, the urine collection catheter 110comprises an elongated tube 12 comprising a proximal portion 14, whichcan be configured for placement in the urethra 128 of the patient, adistal portion 16 comprising a distal end 18, and a sidewall 20extending between a proximal end 22 and the distal end 18 of theelongated tube 12 defining at least one drainage lumen 24 extendingthrough the tube 12. The sidewall 20 of the elongated tube 12 comprisesa drainage portion 26 which allows fluid to pass through the sidewall 20and into the drainage lumen 24.

The elongated tube 12 can have any suitable length to accommodateanatomical differences for gender and/or patient size. In some examples,the tube 12 has a length from about 30 cm to about 120 cm. Further, theelongated tube 1002 can have a maximum outer diameter OD of about 0.25mm to about 10 mm or about 0.33 mm to about 3.0 mm. The elongated tube12 can also have an inner diameter ID of about 0.1 mm to 9.0 mm or about0.16 mm to about 2.40 mm. It is appreciated that the outer and innerdiameters of the elongated tube 12 can include any of the subranges ofthe previously described ranges.

The elongated tube 12 can be formed from any suitable flexible and/ordeformable material. Such materials facilitate advancing and/orpositioning the tube 12 in the bladder 110 or ureters 116, 118.Non-limiting examples of such materials include biocompatible polymers,polyvinyl chloride, polytetrafluoroethylene (PTFE) such as Teflon®,silicon coated latex, or silicon. At least a portion or all of thecatheter device 10, particularly the tube 12, can be coated with ahydrophilic coating to facilitate insertion and/or removal and/or toenhance comfort. In some examples, the coating is a hydrophobic and/orlubricious coating. For example, suitable coatings can compriseComfortCoat® hydrophilic coating which is available from Koninklijke DSMN.V. or hydrophilic coatings comprising polyelectrolyte(s) such as aredisclosed in U.S. Pat. No. 8,512,795, which is incorporated herein byreference. In some examples, the tube 12 is impregnated with or formedfrom a material viewable by fluoroscopic imaging. For example, thebiocompatible polymer which forms the tube 12 can be impregnated withbarium sulfate or a similar radiopaque material. As such, the structureand position of the tube 12 is visible to fluoroscopy.

The drainage portion 26 of the drainage tube 12 can be provided in avariety of configurations depending on the fluid volume and flow rateintended to be drawn into the drainage lumen 24 from the bladder 110.For example, as shown in FIGS. 4A-7B, the drainage portion 26 comprisesat least one fluid port or opening 28 for permitting fluid to flowthrough the sidewall 20 of the tube 12 into the at least one drainagelumen 24. The drainage port(s) or opening(s) 28 can have any shapedesired, such as circular or non-circular, ellipsoid, etc. For example,the opening(s) 28 can be one or more of a circular shape, an ellipticalshape, a square shape, a regular polygonal shape, an irregular circularshape, or an irregular polygonal shape, or combinations thereof. Theport(s) or opening(s) 28 can be have an area of between about 0.02 sq.inches to about 1.0 sq. inches or more. In other examples, the drainageportion 26 of the elongated tube 12 comprises a perforated portion ofsidewall 20 comprising a plurality of perforations.

Desirably, the perforations or fluid openings 28 are positioned so thatnegative pressure provided to the bladder 110 through the drainage lumen24 is evenly distributed through the bladder 110. In some examples, theperforations or openings 28 are positioned so that negative pressure isprovided from the drainage lumen 24 of the elongated tube 12 in alldirections (e.g., so that a 360 degree negative pressure is provided tothe bladder 110). In some examples, a diameter of the openings 28 and/orperforations 30 can range from about 0.005 mm to about 1.0 mm. Theconfiguration of each perforations or opening 28 can be the same ordifferent, as desired. The perforations or openings 28 can be spaced inany arrangement, for example, linear or offset. In some examples, eachport or perforation can be circular or non-circular. In other examples,the drainage portion 26 comprises a mesh material, for example, formedfrom a woven filament and comprising a plurality of openings forconducting fluid from the bladder 110 into the drainage lumen 24 of thetube 12.

With specific reference to FIG. 3, aspects of the proximal portion 14 ofthe elongated tube 12 and external elements of the system 2 aredescribed. The proximal portion 14 of the tube 12 is configured forplacement in a portion of the urinary tract proximal to the bladder,such as the urethra 128. Proximal portions of the elongated tube 12 canalso extend from the body and, for example, can be connected to a fluidcollection container or to the pump 200. In some examples, the proximalportion 14 of the tube 12 is essentially free of or free of openings orperforations. While not intending to be bound by any theory, it isbelieved that when negative pressure is applied at the proximal portion14 of the tube 12, that openings in the proximal portion of the tube 12may be undesirable as such openings may diminish the negative pressureat the distal portion 16 of the urine collection catheter 10 and therebydiminish the draw or flow of fluid or urine from the kidney 112, 116,and renal pelvis 120, 122. It is desirable that the flow of fluid fromthe ureter 114, 116 and/or kidney 112, 114 is not prevented by occlusionof the ureter 116, 118 and/or kidney 112, 114 by the catheter 10.

In some examples, the proximal end 22 of the tube 12 comprises and/or isconnected to a port 32 (shown in FIG. 3) for attaching the catheter 10to the pump 200. The connection between the tube 12 and the pump 200 oranother fluid collection container can be a standard connectionmechanism, such as a luer lock or snap fit connection. In otherexamples, a dedicated or customized connector or connection device canbe used for connecting the proximal end of the catheter device 10 orport 32 to other elements of the fluid collection system. In someexamples, the customized connector can be structured to prevent a userfrom connecting the catheter 10 to unsuitable pressure sources. Forexample, the customized connector may be sized to prevent a user fromconnecting the catheter 10 to sources of wall suction or other sourcesof elevated vacuum pressures.

As described in further detail in connection with FIGS. 13-14B, thefluid pump 200 (shown in FIG. 3) is configured to generate a negativepressure to extract urine from the patient's urinary tract. In someexamples, the pump 200 may also generate a positive pressure and, forexample, may be configured to alternate between providing negativepressure, positive pressure, and equalizing pressure to atmosphere basedon a selection from a user or automatically according to a predeterminedschedule. The pump 200 can be configured to provide a low level negativepressure of 100 mmHg or less to a proximal end of the catheter 10. Insome examples, the pump 200 can be configured to operate at a number ofdiscrete pressure levels. For example, the pump 200 may be configured tooperate at pressure levels of 15 mmHg, 30 mmHg, and 45 mmHg. A user canselect one of the pressure levels using a switch, dial, or controller asare known in the art.

A commercially available pump which can be adapted for use with thesystem 10 is the Air Cadet Vacuum Pump from Cole-Parmer InstrumentCompany (Model No. EW-07530-85). The pump 200 can be connected in seriesto the regulator, such as the V-800 Series Miniature Precision VacuumRegulator—1/8 NPT Ports (Model No. V-800-10-W/K), manufactured byAirtrol Components Inc. Pumps which can be adapted for use with thesystem 200 are also available from Ding Hwa Co., Ltd (DHCL Group) ofDacun, Changhua, China.

In other non-limiting examples, at least a portion of the pump 200 canbe positioned within the patient's urinary tract, for example within thebladder 110. For example, the pump 200 can comprise a pump module and acontrol module coupled to the pump module, the control module beingconfigured to direct motion of the pump module. At least one (one ormore) of the pump module, the control module, or the power supply may bepositioned within the patient's urinary tract. The pump module cancomprise at least one pump element positioned within the fluid flowchannel to draw fluid through the channel. Some examples of suitablepump assemblies, systems and methods of use are disclosed in U.S. PatentApplication No. 62/550,259, entitled “Indwelling Pump for FacilitatingRemoval of Urine from the Urinary Tract”, which is incorporated byreference herein in its entirety.

Tissue Support Structure

Having described elements of the urine collection catheter 10 and pump200, various structures for maintaining the distal portion 16 and distalend 18 of the elongated tube 12 at a desired position in the bladder,ureter, or other positions in the urinary tract will now be discussed indetail. In particular, with reference to FIGS. 4A-7B, the urinecollection catheter 10 further comprises a permeable tissue support 50directly or indirectly connected to the distal portion 16 of theelongated tube 12 and extending axially (e.g., in a direction of arrowA1 in FIG. 4A) and/or radially (e.g., in a direction of arrow A2 in FIG.4A) therefrom. As used herein, the tissue support 50 is directlyconnected to the elongated tube 12 when portions of the tissue supportconnect or are adhered to the tube 12. The tissue support 50 isindirectly connected to the tube 50, when it is connected throughanother fastener, element, or component, such as a sleeve, bracket, orcollar, as are known in the art. The tissue support 50 is configured tobe deployed in the patient's urinary tract to maintain the distal end 18of the elongated tube 12 at a predetermined position in the urinarytract. For example, as shown in FIGS. 1-3, the tissue support 50 isdeployed in the patient's bladder 110. In other examples of a urinecollection catheter, the tissue support 50 can be deployed, for example,in the ureter(s) 116, 118, renal pelvis 120, 122, or kidney(s) 112, 114of the patient. When deployed in the bladder, the permeable tissuesupport 50 can have a maximum outer diameter D1 (in FIG. 4A) of fromabout 10 mm to about 100 mm or about 25 mm to 50 mm and a longitudinallength L1 (in FIG. 4A) of about 10 mm to 100 mm or about 25 mm to 50 mm.In one example, in a retracted position, the tissue support is about 8to about 16 Fr (e.g., about 2.5 mm to about 5 mm) and in the deployedposition is from 10 mm to 100 mm.

When deployed, the permeable tissue support 50 defines athree-dimensional shape of sufficient size to permit flow of at least aportion of fluid from the patient's urinary tract through the tissuesupport 50 and drainage portion 26 of the elongated tube 12 to the atleast one drainage lumen 24. For instance, when deployed in the bladder110, the tissue support 50 can be configured to inhibit mucosal oruroendothelium tissue of the bladder 110 from occluding at least aportion of the tissue support 50 or drainage portion 26 of the tube 12.When deployed in other portions of the urinary tract, the tissue support50 can be sized to maintain patency of fluid through the tissue support50 to the drainage portion 26 of the tube 12 in a patient's kidney(s)112, 114, ureter(s) 116, 118, and/or in the renal pelvis 120, 122.

When configured to be deployed in the bladder 110, the three-dimensionalshape enclosed by the tissue support 50 has a volume of from about 10cm³ to about 500 cm³. When used in the ureter(s) 116, 118, renal pelvis120, 122, or kidney 112, 114, the volume of the tissue support 50 isfrom about 0.10 cm³ to about 100 cm³. As used herein, thethree-dimensional shape is defined as a regular shape (e.g., a sphere,cylinder, pyramid, cube, or triangular prism) defined by outer surfacesof the tissue support 50. For example, if the tissue support 50comprises a spherical outer surface (e.g., a spherical balloon) having aradius (r), then a volume (V) of the three dimensional shape is

$V = {\frac{4}{3}\pi\;{r^{3}.}}$In a similar manner, a tissue support 50 formed by axially or radiallyextending filaments or wires which outline a sphere of radius (r) alsohas a volume (V) of

${V = {\frac{4}{3}\pi\; r^{3}}},$even when the tissue support 50 is not a fully enclosed shape.

When deployed, the permeable tissue support 50 is configured to maintaina volume of the three dimensional shape when portions of the urinarytract contract around the tissue support 50. For example, when aninterior of the bladder 110 is exposed to an internal negative pressure,portions of the superior and inferior bladder walls 100 a, 100 bcontract and come into contact with the tissue support 50. The tissuesupport 50 should provide sufficient structure to prevent or inhibitsuch portions of the bladder wall 100 a, 100 b from occluding theureters 116, 118 and ureteral orifices or openings 124, 126 so thatfluid and urine continue to travel through the ureters 126, 128 and intothe bladder 110. In a similar manner, the ureteral orifices or openings124, 126 and ureters 126, 128 should remain open so that internalnegative pressure applied in the bladder 110 is transferred from thebladder 110, through the ureters 116, 118 and to the kidneys 112, 114.As discussed above, while not intending to be bound by theory, it isbelieved that applying internal negative pressure to the kidneys 112,114 induces urine production to achieve desired therapeutic results. Inview of the need to maintain open fluid flow into the bladder 110, ashape and size of the deployed tissue support 50 is selected to preventportions of the bladder 110 in proximity to the ureteral orifices oropenings 124, 126 from collapsing or occluding. For example, the tissuesupport 50 can be shaped so that, when deployed, a widest portion of thetissue support 50 is adjacent to the orifices or openings 124, 126 toprevent such portions of the bladder 110 from collapsing.

The tissue support 50 also desirably provides sufficient structuralsupport so that openings 28 of the drainage portion 26 of the tube 12are not occluded by tissues of the bladder wall when negative pressureis delivered to the bladder. Specifically, as described above, while notintending to be bound by theory, it is believed that upon delivery ofnegative pressure, the bladder wall contracts around the tissue support50, as shown by the empty bladder E in FIGS. 2 and 3. The tissue support50 should provide sufficient structure to resist such contraction toprevent or inhibit portions of the bladder wall from collapsing thetissue support 50 and contracting against the drainage portion 26 of thetube 12, which would prevent fluid and urine from flowing through thetissue support 50 and into the drainage lumen 24 of the tube 12.Further, in some examples, the tissue support 50 is desirably formedfrom a material that does not appreciably abrade, irritate, or damage amucosal lining of the bladder wall or other portions of the urinarytract when positioned adjacent to the mucosal lining of the bladder wallor the urethra.

In addition to providing sufficient structural support to maintainpatency of fluid or urine from the kidneys 112, 116 through theureter(s) 116, 118, and bladder 100, and into the drainage lumen 24 ofthe tube 12, the permeable tissue support 50 is also formed from amaterial capable of permitting fluid to pass therethrough. Morespecifically, as used herein, a permeable support is a support whichpermits fluid, such as urine, to pass from a portion of urinary tract,such as the bladder 110, through the tissue support 50 and into thedrainage lumen 24 of the drainage tube 12.

In some examples, in order to provide such permeability, the permeabletissue support 50 is formed from one of biocompatible polymer fiber(s);metallic fiber(s), porous film(s), film(s) comprising one or moreapertures, fabric(s), or any combination thereof. The support generallyhas a thickness of from about 0.5 mm to about 5 mm. In other examples,the permeable tissue support 50 comprises plurality of elongatedmembers, such as wire filaments 52, having a first end 54 and/or asecond end 56 connected to the elongated tube 12 and woven together toform a wire filament mesh. The elongated members or wire filaments 52can be formed from any suitable material which provides sufficientstructural support to prevent tissues of the urinary tract fromoccluding the drainage portion 26 of the tube 12, such as one or more ofbiocompatible plastics, such as polyethylene, and/or metal, such asnitinol. In one example, the elongated members or wire filaments 52 area nitinol monofilament wire. The filament may have a diameter of about25 μm to about 5 mm or about 100 μm to about 1.5 mm. In some examples,an outer surface of the tissue support 50 is primarily formed from acontinuous surface, as is the case for a support 50 formed from a filmwith only a small number of openings for permitting fluid to passthrough the support 50 toward the drainage portion 26. In otherexamples, such as in embodiments formed from a wire filament mesh, thetissue support is primarily an open structure in which only a smallportion of the outer surface of the support 50 is covered by wirefilaments 52. In either case, desirably, a total surface area ofopenings of the tissue support member is at least equal to a totalsurface area of the opening 28 or perforations 30 of the drainageportion 26 of the tube 12 to permit sufficient fluid flow into thedrainage lumen 14.

The tissue support 50 can be mounted to the tube 12 using a variety ofdifferent types of fasteners, adhesives, brackets, and other mechanisms.For example, the tissue support 50 can be connected to the elongatedtube 12 by one or more mechanical connectors, such as an annular collar58, 60 or cap. In that case, portions of the mesh, such as wirefilaments or elongated members 52, are crimped against the elongatedtube 12 at a desired position and locked in place by the collar 58 orcap. In this way, the collar 58, 60 effectively mounts the crimpedportions of the elongated members or wire filaments 52 to the tube 12,thereby fixedly attaching the elongated members or wire filaments 52 tothe tube 12.

In other examples, wire filaments 52 of the tissue support 50 can beconnected to the tube 12 through the collar 58. In that case, the collar58 can be configured to slide along the elongated tube 12 to deploy thetissue support 50 and/or to adjust sizing of the tissue support 50 bysliding the collar 58 toward the distal end 18 of the tube 12 (toincrease a maximum outer diameter of the tissue port) or proximally toretract or reduce the maximum outer diameter of the tissue support.

In order to facilitate placement and removal of the urine collectioncatheter 10, the permeable tissue support 50 is configured to transitionfrom a retracted position (shown in FIG. 5B) to a deployed position(shown in FIGS. 4A, 4B, and 5A). For example, the tissue support 50 canbe maintained in a retracted position by a delivery catheter 90. Thedelivery catheter 90 generally comprises a tubular structure sized toreceive at least a portion of the elongated tube 12 and the tissuesupport 50. The delivery catheter 90 may comprise a proximal end (notshown) configured to be located outside of the body, an open distal end92 configured to be advanced through the urinary tract to the urethra orbladder 110, and a sidewall 94 expending therebetween. As was the casewith the elongated tube 12, the length of the delivery catheter 90 isvariable depending on age and gender of the patient. Generally, a lengthof a sterile portion of the delivery catheter 90 is about 1 in to 3inches for women, to about 20 inches for men. The total length of thedelivery catheter 90 including sterile and non-sterile portions can beseveral feet. The diameter of the delivery catheter 90 is generallyslightly larger than the outer diameter of the elongated tube 12. Forexample, the delivery catheter 90 may be about 10 Fr to about 26 Fr.When retracted, the tissue support 50 is radially compressed such thatan outer diameter of the retracted tissue support 50 is defined by aninner diameter ID of the delivery sheath or catheter 90, as shown inFIG. 5B.

As described in further detail in connection with FIGS. 9 and 10, thecatheter 10 and tissue support 50 are deployed through the deliverycatheter 90. Specifically, the tissue support 50 is maintained in itsretracted position by the delivery catheter 90 and is advanced throughthe urinary tract to the bladder. In the bladder, the delivery catheter90 is retracted to release the tissue support 50. Once the tissuesupport 50 is clear of the open distal end 92 of the delivery catheter90 it can be biased to adopt the deployed position. At this point, thetissue support 50 generally floats freely within the bladder 110. Whennegative pressure is applied to the bladder 110, portions of the bladderwall are drawn against the tissue support 50. The bladder wall isprevented from occluding the drainage portion 26 of the elongated tube12 by the tissue support 50. When ready to remove the distal portion 16of the catheter 10 from the patient's bladder 110, a user retracts thetissue support 50 into the delivery catheter 90 causing the tissuesupport 50 to return to its retracted position. Once in the retractedposition and enclosed in the delivery catheter 90, the user draws thedelivery catheter 90 and urine collection catheter 10 from the urinarytract by, for example, pulling the delivery catheter 60 and structurescontained therein through the urethra and from the body.

In other examples, the urine collection catheter 10 can includeconcentric slidable elongated tubes, in which a first portion of thetissue support 50 is mounted to a first or inner tube and a secondportion of the tissue support is mounted to a second or outer tube. Inthat case, extending the inner tube through an open distal end of theouter tube causes deployment of the tissue support 50. Retracting theinner tube back into the outer tube causes the tissue support 50 toretract.

Having described the general structure of portions of the catheter 10including the elongated tube 12 and tissue support 50, specific shapesof tissue supports 50 which can be used when providing negative pressuretherapy to a patient will now be described in detail. As shown in FIGS.4A-7B, these structures are each formed from elongated members orflexible wires 52 woven together to form a tissue support 50 havingsufficient structural strength to counteract forces exerting by acontracting bladder 110 and sufficient permeability such that fluid orurine passes through the tissue support 50 and to the drainage portion26 of the elongated tube 12.

In some examples, as shown in FIGS. 4A and 4B, the tissue support 50comprises a substantially cylindrical distal portion 64 and taperedproximal portion 66. The substantially cylindrical distal portion 64defines a substantially flat and circular distal surface 68. The tissuesupport 50 is formed from a mesh formed from the woven elongated members52. The embodiment of FIGS. 4A and 4B includes a collar 58 which mountsproximal ends 54 of the elongated members or filament wires 52 to theelongated tube 12 and a collar 60 which mounts distal ends 56 of theelongated members to the tube 12. As shown in FIG. 4B, the drainageportion 26 of the tube extends distally beyond the collar 58 and is atleast partially enclosed by the tissue support 50. The drainage portion26 includes an opening 28. In other examples, as described above, thedrainage portion 26 could include multiple openings 28 or perforations.The tissue support 50, shown in FIGS. 4A and 4B, is shown in a retractedstate within a drainage catheter 90 in FIG. 5B.

With reference to FIGS. 6A and 6B, another embodiment of a permeabletissue support 50 of a urine collection catheter 10 is illustrated. Thetissue support 50 can be formed from elongated members or wire filaments52 woven together, as in previously described examples. The support 50includes collars 58, 60 located at both the proximal and distal ends ofthe tissue support 50. Further, the elongated tube 12 extends throughthe entire tissue support 50, from a proximal end 70 to a distal end 72thereof. As shown in FIGS. 6A and 6B, when deployed, a middle portion 74of the permeable tissue support 50 bulges radially outward from proximaland distal portions 64, 66 thereof, such that an outer diameter of thepermeable tissue support 50 increases from the proximal end 70 to themiddle portion 74 thereof and decreases from the middle portion 74 tothe distal end 72 thereof. A maximum outer diameter D2 of the middleportion 74 of the tissue support 50 can be from 5 mm to 40 mm, whenconfigured to be deployed in the bladder 110. The tissue support 50 canhave a longitudinal length L2 of from about 5 mm to about 40 mm. As inprevious examples, the drainage portion 26 of the elongated tube 12including openings 28 is at least partially enclosed by the tissuesupport 50. In other examples, openings 28 could be replaced by asection of tubing comprising perforations 30 as described previously.

With reference to FIGS. 7A and 7B, in another example, the permeabletissue support 50 comprises a narrow middle portion 74 between widerproximal and distal portions 64, 66. As in previous examples, the tissuesupport 50 has a maximum outer diameter D3 of from 10 mm to 100 mm, whenconfigured to be deployed in a patient's bladder. In some examples, asshown in FIGS. 7A and 7B, the narrow middle portion 74 has a minimumouter diameter equal to or substantially equal to an outer diameter ofthe elongated tube 12, such that the distal portion 64 of the tissuesupport 50 is separate or spaced apart from the proximal portion 66,such that both the proximal portion 66 and the distal portion 64 have alength L3. The length L3 of the portions can be from about 2.5 mm toabout 50 mm, when configured to be deployed in the bladder. In theconfiguration shown in FIGS. 7A and 7B, the tissue support 50 is sizedsuch that, when deployed in the patient's bladder, the distal portion 64extends beyond the trigone region and ureteral openings of the bladder110. For example, the distal portion 64 can be sized to support thesuperior bladder wall when the bladder is empty. The proximal portion 66can be positioned between the urethral opening and the ureteralopenings. In this configuration, the proximal and distal portions 64, 66provide support for portions of the bladder wall both above and belowthe ureteral openings. As such, the proximal and distal portions 64, 66of the tissue support 50, desirably, counteract contraction of bothsuperior and inferior walls of the bladder 110 to prevent portions ofthe contracted bladder wall from occluding or closing the ureteralorifices or openings.

In some examples, as shown in FIGS. 7A and 7B, the narrow middle portion74 is formed by a metal collar 62 or crimped portion which holds orattaches middle portions of the elongated members or wire filaments 52against the elongated tube 12. As such, as shown in FIGS. 7A and 7B, theproximal portion 66 and the distal portion 64 of the tissue support 50are spaced apart and separated by the collar 62. Drainage portions 26 ofthe tube 12 can be enclosed in both the proximal and distal portions 64,66 of the tissue support 50. For example, as shown in FIG. 7B, openings28 are enclosed by each structure.

In other examples, the woven elongated members or wire filaments 52 maybe biased or molded to form the narrow middle portion 74 of the tissuesupport 50, when the tissue support is deployed. For example, a heatsetting process may be applied to the elongated members or wirefilaments so that they conform to a desired shape. In some examples, asshown in FIGS. 7A and 7B, the narrow middle portion 74 extends all theway to the elongated tube (e.g., the narrow middle portion 74 has aminimum outer diameter equal to an outer diameter of the elongated tube12). In other examples, the narrow middle portion 74 is an annulargroove extending radially inwardly from other portions of the tissuesupport 50. For example, the groove may have a depth relative to themaximum outer diameter D3 of the tissue support 50, of from about 2.5 mmto about 10 mm. In a similar manner, the middle annular portion may havea minimum outer diameter of from about 10% to about 99% less than amaximum outer diameter of the permeable tissue support.

Ureteral Stents

As discussed above, the urine collection catheters 10 disclosed hereincan be used to apply negative pressure therapy to increase renalperfusion. As such, negative pressure delivered through a urinecollection catheter 10 deployed in the bladder 110 must transfer throughthe ureters 116, 118 to the kidneys 112, 114. In some examples, ureteralstents 352, 354 can be inserted through the ureters 116, 118 to maintainpatency of the ureters 116, 118 and to ensure that the ureteral orificesor openings 124, 126 remain open upon application of negative pressureto the bladder.

As used herein, “maintain patency of fluid flow between a kidney and abladder of the patient” means establishing, increasing or maintainingflow of fluid, such as urine, from the kidneys through the ureter(s),ureteral stent(s) and/or ureteral catheter(s) to the bladder. As usedherein, “fluid” means urine and any other fluid from the urinary tract.

An exemplary urine collection system including the urine collectioncatheter 10, permeable tissue support 50 deployed in the bladder, andthe ureteral stents 352, 354 is shown in FIG. 8. The stent 352 isdeployed in the right ureter 116, such that a distal end or retentionportion of the stent 352 extends to the right kidney 112, or to therenal pelvis 120 adjacent to the right kidney 112. The ureteral stent354 is deployed in the left ureter 118, such that a distal end of thestent 354 extends to the left renal pelvis 122 or left kidney 114.Typically, these stents 352, 354 are deployed by inserting a stenthaving a nitinol wire therethrough through the urethra 128 and bladder110 up to the kidney 112, 114, then withdrawing the nitinol wire fromthe stent 352, 354, which permits the stent to assume a deployedconfiguration. Many of the above stents have a planar loop 358, 360 onthe distal end (to be deployed in the kidney), and some also have aplanar loop 362, 364 on the proximal end of the stent which is deployedin the bladder. When the nitinol wire is removed, the stent assumes thepre-stressed planar loop shape at the distal and/or proximal ends. Toremove the stent 352, 354, a nitinol wire is inserted to straighten thestent and the stent is withdrawn from the ureter and urethra.

Some examples of ureteral stents 352, 354 that can be useful in thepresent systems and methods include CONTOUR™ ureteral stents, CONTOURVL™ ureteral stents, POLARIS™ Loop ureteral stents, POLARIS™ Ultraureteral stents, PERCUFLEX™ ureteral stents, PERCUFLEX™ Plus ureteralstents, STRETCH™ VL Flexima ureteral stents, each of which arecommercially available from Boston Scientific Corporation of Natick,Mass. See “Ureteral Stent Portfolio”, a publication of Boston ScientificCorp., (July 2010), hereby incorporated by reference herein. TheCONTOUR™ and CONTOUR VL™ ureteral stents are constructed with softPercuflex™ Material that becomes soft at body temperature and isdesigned for a 365-day indwelling time. Variable length coils on distaland proximal ends allow for one stent to fit various ureteral lengths.The fixed length stent can be 6 F-8 F with lengths ranging from 20 cm-30cm, and the variable length stent can be 4.8 F-7 F with lengths of 22-30cm. Other examples of suitable ureteral stents include INLAY® ureteralstents, INLAY® OPTIMA® ureteral stents, BARDEX® double pigtail ureteralstents, and FLUORO-4™ silicone ureteral stent, each of which arecommercially available from C.R. Bard, Inc. of Murray Hill, N.J. See“Ureteral Stents”,http://www.bardmedical.com/products/kidney-stone-management/ureteral-stents/(Jan. 21, 2018), hereby incorporated by reference herein.

The stents 352, 354 can be deployed in one or both of the patient'skidneys or kidney area (renal pelvis or ureters adjacent to the renalpelvis), as desired. Typically, these stents are deployed by inserting astent having a nitinol wire therethrough through the urethra and bladderup to the kidney, then withdrawing the nitinol wire from the stent,which permits the stent to assume a deployed configuration. Many of theabove stents have a planar loop 358, 360 on the distal end (to bedeployed in the kidney), and some also have a planar loop 362, 364 onthe proximal end of the stent which is deployed in the bladder. When thenitinol wire is removed, the stent assumes the pre-stressed planar loopshape at the distal and/or proximal ends. To remove the stent, a nitinolwire is inserted to straighten the stent and the stent is withdrawn fromthe ureter and urethra.

Other examples of suitable ureteral stents 352, 354 are disclosed in PCTPatent Application Publication WO 2017/019974, which is incorporated byreference herein. In some examples, as shown, for example, in FIGS. 1-7of WO 2017/019974 and in FIG. 9 herein (same as FIG. 1 of WO2017/019974). As shown in FIG. 9, the exemplary ureteral stent 1000 theureteral stent 1000 can comprise: an elongated body 1001 comprising aproximal end 1002, a distal end 1004, a longitudinal axis 1006, an outersurface 1008, and an inner surface 1010, wherein the inner surface 1010defines a transformable bore 1011 that extends along the longitudinalaxis 1006 from the proximal end 1002 to the distal end 1004; and atleast two fins 1012 projecting radially away from the outer surface 1008of the body 1001; wherein the transformable bore 1011 comprises: (a) adefault orientation 1013A (shown on the left in FIG. 9) comprising anopen bore 1014 defining a longitudinally open channel 1016; and (b) asecond orientation 1013B (shown on the right in FIG. 9) comprising an atleast essentially closed bore 1018 or closed bore defining alongitudinally essentially closed drainage channel 1020 along thelongitudinal axis 1006 of the elongated body 1001, wherein thetransformable bore 1011 is moveable from the default orientation 1013Ato the second orientation 1013B upon radial compression forces 1022being applied to at least a portion of the outer surface 1008 of thebody 1001.

In some examples, as shown in FIG. 9, the drainage channel 1020 of theureteral stent 1000 has a diameter D which is reduced upon thetransformable bore 1011 moving from the default orientation 1013A to thesecond orientation 1013B, wherein the diameter is reducible up to thepoint above where urine flow through the transformable bore 1011 wouldbe reduced. In some examples, the diameter D is reduced by up to about40% upon the transformable bore 1011 moving from the default orientation1013A to the second orientation 1013B. In some examples, the diameter Din the default orientation 1013A can range from about 0.75 to about 5.5mm, or about 1.3 mm or about 1.4 mm. In some examples, the diameter Dinthe second orientation 1013B can range from about 0.4 to about 4 mm, orabout 0.9 mm.

In some examples, one or more fins 1012 comprise a flexible materialthat is soft to medium soft based on the Shore hardness scale. In someexamples, the body 1001 comprises a flexible material that is mediumhard to hard based on the Shore hardness scale. In some examples, one ormore fins have a durometer between about 15 A to about 40 A. In someexamples, the body 1001 has a durometer between about 80 A to about 90A. In some examples, one or more fins 1012 and the body 1001 comprise aflexible material that is medium soft to medium hard based on the Shorehardness scale, for example having a durometer between about 40 A toabout 70 A.

In some examples, one or more fins 1012 and the body 1001 comprise aflexible material that is medium hard to hard based on the Shorehardness scale, for example having a durometer between about 85 A toabout 90 A.

In some examples, the default orientation 1013A and the secondorientation 1013B support fluid or urine flow around the outer surface1008 of the stent 1000 in addition to through the transformable bore1011.

In some examples, one or more fins 1012 extend longitudinally from theproximal end 1002 to the distal end 1004. In some examples, the stenthas two, three or four fins.

In some examples, the outer surface 1008 of the body has an outerdiameter in the default orientation 1013A ranging from about 0.8 mm toabout 6 mm, or about 3 mm. In some examples, the outer surface 1008 ofthe body has an outer diameter in the second orientation 1013B rangingfrom about 0.5 mm to about 4.5 mm, or about 1 mm. In some examples, oneor more fins have a width or tip ranging from about 0.25 mm to about 1.5mm, or about 1 mm, projecting from the outer surface 1008 of the body ina direction generally perpendicular to the longitudinal axis.

In some examples, the radial compression forces are provided by at leastone of normal ureter physiology, abnormal ureter physiology, orapplication of any external force. In some examples, the ureteral stent1000 purposefully adapts to a dynamic ureteral environment, the ureteralstent 1000 comprising: an elongated body 1001 comprising a proximal end1002, a distal end 1004, a longitudinal axis 1006, an outer surface1008, and an inner surface 1010, wherein the inner surface 1010 definesa transformable bore 1011 that extends along the longitudinal axis 1006from the proximal end 1002 to the distal end 1004; wherein thetransformable bore 1011 comprises: (a) a default orientation 113Acomprising an open bore 114 defining a longitudinally open channel 116;and (b) a second orientation 1013B comprising an at least essentiallyclosed bore 1018 defining a longitudinally essentially closed channel1020, wherein the transformable bore is moveable from the defaultorientation 1013A to the second orientation 1013B upon radialcompression forces 1022 being applied to at least a portion of the outersurface 1008 of the body 1001, wherein the inner surface 1010 of thebody 1001 has a diameter D which is reduced upon the transformable bore1011 moving from the default orientation 1013A to the second orientation1013B, wherein the diameter is reducible up to the point above wherefluid flow through the transformable bore 1011 would be reduced. In someexamples, the diameter D is reduced by up to about 40% upon thetransformable bore 1011 moving from the default orientation 1013A to thesecond orientation 1013B.

Other examples of suitable ureteral stents are disclosed in UnitedStates Patent Application Publication No. 2002/0183853 A1, which isincorporated by reference herein. In some examples, as shown, forexample, in FIGS. 4, 5 and 7 of US 2002/0183853 A1 and in FIGS. 4-6herein (same as FIGS. 1 of 4, 5 and 7 of US 2002/0183853 A1), theureteral stent comprises an elongated, body 10 comprising a proximal end12, a distal end 14 (not shown), a longitudinal axis 15, and at leastone drainage channel (for example, 26, 28, 30 in FIGS. 4; 32, 34, 36 and38 in FIG. 5; and 48 in FIG. 6) that extends along the longitudinal axis15 from the proximal end 12 to the distal end 14 to maintain patency offluid flow between a kidney and a bladder of the patient. In someexamples, the at least one drainage channel is partially open along atleast a longitudinal portion thereof. In some examples, the at least onedrainage channel is closed along at least a longitudinal portionthereof. In some examples, the at least one drainage channel is closedalong the longitudinal length thereof. In some examples, the ureteralstent is radially compressible. In some examples, the ureteral stent isradially compressible to narrow the at least one drainage channel. Insome examples, the elongated body 10 comprises at least one external fin40 along the longitudinal axis 15 of the elongated body 10. In someexamples, the elongated body comprises one to four drainage channels.The diameter of the drainage channel can be the same as described above.

With reference to FIG. 10A, other embodiments of exemplary ureteralstents 352, 354 which can be used within the scope of the presentdisclosure to maintain patency of fluid from the kidneys 112, 114 andthe ureters 116, 118 to the bladder 110 comprises an elongated tube,which extends from a retention portion located in the bladder. Thestents 352, 354 include a helical retention portion 430 comprising aplurality of coils 432 which maintains a distal end the tube in adesired position in a patient's renal pelvis 120, 122 or kidney 112,114. For example, as described in further detail in connection withFIGS. 10B and 10C, the helical retention portion 432 can comprise atleast a first coil having a first diameter; at least a second coilhaving a second diameter, the first diameter being less than the seconddiameter, the second coil being closer to an end of the distal portionof the drainage lumen than the first coil; and one or more perforationson a sidewall of the coiled retention portion of the distal portion ofthe drainage lumen for permitting fluid flow into the drainage lumen. Insome examples, the helical stents 352, 354 could be configured suchthat, prior to insertion into a patient's urinary tract, a portion ofthe drainage lumen that is proximal to the retention portion defines astraight or curvilinear central axis, and wherein, when deployed, thefirst coil and the second coil of the retention portion extend about anaxis of the retention portion that is at least partially coextensivewith the straight or curvilinear central axis of the portion of thedrainage lumen.

As shown in FIGS. 10B and 10C, an exemplary retention portion 430comprising a plurality of helical coils, which can be used to anchor theureteral stents disclosed herein are illustrated. The retention portions430 generally comprise one or more full coils 484 and one or more halfor partial coils 483. The retention portion 430 is capable of movingbetween a contracted position and the deployed position with theplurality of helical coils. For example, a substantially straightguidewire can be inserted through the retention portion 430 to maintainthe retention portion 430 in a substantially straight contractedposition. When the guidewire is removed, the retention portion 430 cantransition to its coiled configuration. In some examples, the coils 483,484 extend radially and longitudinally from the distal portion 418 ofthe tube 412. In a preferred exemplary embodiment, the retention portion430 comprises two full coils 484 and one half coil 483. The outerdiameter of the full coils 484, shown by line D4, can be about 18±2 mm.The half coil 483 diameter D5 can be about 14 mm±2 mm. The retentionportion 430 can further comprise the one or more drainage holes 432configured to draw fluid into an interior of the elongated tube 412 ofthe stent.

Ureteral Catheters

The urine collection catheter 10 tissue support 50 disclosed herein anddescribed in detail in connection with FIGS. 1-7B can also be adoptedfor use as a ureteral catheter in which the tissue support 50 isdeployed in the renal pelvis 120, 122 or kidney 112, 114 adjacent to therenal pelvis 120, 122. The elongated tube 12 can extend from the tissuesupport 50, through the patient's ureter 116, 118, bladder 110, urethra128, and from the body as shown in FIG. 11. The ureteral catheters canbe connected to the pump 200 using conventional connectors, such as luerfittings, snap connectors, and similar mechanisms, as are known in theart. In other examples, as shown in FIG. 11, the ureteral catheters 10can be connected to the pump 200 through a y-connector.

In order to adopt the urine collection catheters 10 disclosed above foruse as ureteral catheters, the dimensions of the catheter 10 and tissuesupport 50 are adjusted to fit within the renal pelvis and/or kidneyadjacent to the renal pelvis. In addition, a cross-sectional shape ofthe tissue support 50 may need to be adjusted to fit within the renalpelvis and/or to ensure that the ureter remains open between the kidneyand bladder when an interior negative pressure is applied to the kidneythrough the ureteral catheter. For example, since the renal pelvis is acornucopia shaped structure, a cross sectional shape of the tissuesupport could be selected having a similar cornucopia shape. Inaddition, the drainage portion of the elongated tube may be curved tocorrespond to a curvature of the cornucopia shaped renal pelvis.

In some examples, when configured to be deployed in the renal pelvis120, 122 or kidneys 112, 114, as shown in FIG. 11, the tissue support 50can have a maximum outer diameter of about 1.5 mm to about 25 mm and alength of about 1.5 mm to about 25 mm. A volume of a three dimensionalshape defined by the tissue support 50, when configured for deploymentin the renal pelvis or kidney is from about 0.1 cm³ to about 25 cm³.

With reference to FIG. 12A, steps for positioning a fluid collectionassembly in a patient's body and, optionally, for inducing negativepressure in a patient's ureter and/or kidneys are illustrated. As shownat box 610, a medical professional or caregiver inserts a flexible orrigid cystoscope through the patient's urethra and into the bladder toobtain visualization of the ureteral orifices or openings. Once suitablevisualization is obtained, as shown at box 612, a guidewire is advancedthrough the urethra, bladder, ureteral opening, ureter, and to a desiredfluid collection position, such as the renal pelvis of the kidney. Oncethe guidewire is advanced to the desired fluid collection position, aureteral catheter of the present invention (examples of which arediscussed in detail above) is inserted over the guidewire to the fluidcollection position, as shown at box 614. In some examples, the locationof the ureteral catheter can be confirmed by fluoroscopy, as shown atbox 616. Once the position of the distal end of the catheter isconfirmed, as shown at box 618, the retention portion of the ureteralcatheter can be deployed. For example, the guidewire can be removed fromthe catheter, thereby allowing the distal end and/or retention portionto transition to a deployed position. In some examples, the deployeddistal end portion of the catheter does not entirely occlude the ureterand/or renal pelvis, such that urine is permitted to pass outside thecatheter and through the ureters into the bladder. Since moving thecatheter can exert forces against urinary tract tissues, avoidingcomplete blockage of the ureters avoids application of force to theureter sidewalls, which may cause injury.

After the ureteral catheter is in place and deployed, the same guidewirecan be used to position a second ureteral catheter in the other ureterand/or kidney using the same insertion and positioning methods describedherein. For example, the cystoscope can be used to obtain visualizationof the other ureteral opening in the bladder, and the guidewire can beadvanced through the visualized ureteral opening to a fluid collectionposition in the other ureter. A catheter can be drawn alongside theguidewire and deployed in the manner described herein. Alternatively,the cystoscope and guidewire can be removed from the body. Thecystoscope can be reinserted into the bladder over the first ureteralcatheter. The cystoscope is used, in the manner described above, toobtain visualization of the ureteral opening and to assist in advancinga second guidewire to the second ureter and/or kidney for positioning ofthe second ureteral catheter. Once the ureteral catheters are in place,in some examples, the guidewire and cystoscope are removed. In otherexamples, the cystoscope and/or guidewire can remain in the bladder toassist with placement of the bladder catheter.

A bladder catheter can also be used either as the only source ofnegative pressure (as in the examples described in connection with FIGS.1-10) or to provide an additional drainage conduct for the fluidcollection system of FIG. 11. In some examples, the bladder catheter isinserted without use of a cystoscope or other imaging apparatus.Instead, the bladder catheter is merely inserted in its collapsed statethrough the urethra and into the bladder. The bladder catheter isdeployed by retracting the deployment catheter as described above. Inother examples, the bladder catheter is inserted over the same guidewireused to position the ureteral catheters.

When used in combination with urine collection catheters deployed in theureters (as shown in FIG. 11), the bladder catheter can be either aconventional Foley bladder catheter or a bladder catheter of the presentinvention as discussed in detail above. In any case, once inserted inthe bladder, as shown at box 622, an anchor of a Foley catheter or thetissue support is expanded to a deployed position. For example, when anexpandable or inflatable catheter is used, fluid may be directed throughan inflation lumen of the bladder catheter to expand a balloon structurelocated in the patient's bladder. In some examples, the urine ispermitted to drain by gravity from the urethra. In other examples, anegative pressure is induced in the ureteral catheter and/or bladdercatheter to facilitate drainage of the urine.

With reference to FIG. 12B, steps for using the urine collectionassembly for inducement of negative pressure in the ureter(s) and/orkidney(s) are illustrated. As shown at box 624, after the indwellingportions of the bladder and/or ureteral catheters are correctlypositioned and anchoring/retention structures are deployed, the externalproximal ends of the catheter(s) are connected to fluid collection orpump assemblies. For example, the ureteral catheter(s) can be connectedto a pump for inducing negative pressure at the patient's renal pelvisand/or kidney. In a similar manner, the bladder catheter can beconnected directly to a urine collection container for gravity drainageof urine from the bladder or connected to a pump for inducing negativepressure at the bladder.

Once the catheter(s) and pump assembly are connected, negative pressureis applied to the renal pelvis and/or kidney and/or bladder through thedrainage lumens of the ureteral catheters and/or bladder catheter, asshown at box 626. The negative pressure is intended to countercongestion mediated interstitial hydrostatic pressures due to elevatedintra-abdominal pressure and consequential or elevated renal venouspressure or renal lymphatic pressure. The applied negative pressure istherefore capable of increasing flow of filtrate through the medullarytubules and of decreasing water and sodium re-absorption.

In some examples, mechanical stimulation can be provided to portions ofthe ureters and/or renal pelvis to supplement or modify therapeuticaffects obtained by application of negative pressure. For example,mechanical stimulation devices, such as linear actuators and other knowndevices for providing, for example, vibration waves, disposed in distalportions of the ureteral catheter(s) can be actuated. While notintending to be bound by theory, it is believed that such stimulationeffects adjacent tissues by, for example, stimulating nerves and/oractuating peristaltic muscles associated with the ureter(s) and/or renalpelvis. Stimulation of nerves and activation of muscles may producechanges in pressure gradients or pressure levels in surrounding tissuesand organs which may contribute to or, in some cases, enhancetherapeutic benefits of negative pressure therapy. In some examples, themechanical stimulation can comprise pulsating stimulation. In otherexamples, low levels of mechanical stimulation can be providedcontinuously as negative pressure is being provided through the ureteralcatheter(s). In other examples, inflatable portions of the ureteralcatheter could be inflated and deflated in a pulsating manner tostimulate adjacent nerve and muscle tissue, in a similar manner toactuation of the mechanical stimulation devices described herein.

As a result of the applied negative pressure, as shown at box 628, urineis drawn into the catheter at the plurality of drainage ports oropenings at the distal end thereof, through the drainage lumen of thecatheter, and to a fluid collection container for disposal. As the urineis being drawn to the collection container, at box 630, sensors disposedin the fluid collection system provide a number of measurements aboutthe urine that can be used to assess the volume of urine collected, aswell as information about the physical condition of the patient andcomposition of the urine produced. In some examples, the informationobtained by the sensors is processed, as shown at box 632, by aprocessor associated with the pump and/or with another patientmonitoring device and, at box 634, is displayed to the user via a visualdisplay of an associated feedback device.

Exemplary Fluid Collection System

Having described an exemplary urine collection devices, systems, andmethod of positioning such an assembly in the patient's body, withreference to FIG. 13, a system 700 for inducing negative pressure to apatient's ureter(s) and/or kidney(s) will now be described. The system700 can comprise the ureteral catheter(s), bladder catheter or the urinecollection assembly 100 described hereinabove. As shown in FIG. 13,urine collection catheter 10 comprising the tissue support 50 isconnected to one or more fluid collection containers 712 for collectingurine drawn from the renal pelvis and/or bladder. The fluid collectioncontainer 712 connected to the urine collection catheter 10 can be influid communication with an external fluid pump 710 for generatingnegative pressure in the ureter(s) and kidney(s) through the catheter10. The pump 710 can be the pump 200 shown in FIGS. 3 and 8. In otherexamples, the pump 710 can be a vacuum pump, rotary pump, or othernegative pressure source, as is known in the art. As discussed herein,such negative pressure can be provided for overcoming interstitialpressure and forming urine in the kidney or nephron. In some examples, aconnection between the fluid collection container 712 and pump 710 cancomprise a fluid lock or fluid barrier to prevent air from entering therenal pelvis or kidney in case of incidental therapeutic ornon-therapeutic pressure changes. For example, inflow and outflow portsof the fluid container can be positioned below a fluid level in thecontainer. Accordingly, air is prevented from entering medical tubing orthe catheter through either the inflow or outflow ports of the fluidcontainer 712. As discussed previously, external portions of the tubingextending between the fluid collection container 712 and the pump 710can include one or more filters to prevent urine and/or particulatesfrom entering the pump 710.

As shown in FIG. 13, the system 700 further comprises a controller 714,such as a microprocessor, electronically coupled to the pump 710 andhaving or associated with computer readable memory 716. In someexamples, the memory 716 comprises instructions that, when executed,cause the controller 714 to receive information from sensors 174 locatedon or associated with portions of the catheter 10. Information about acondition of the patient can be determined based on information from thesensors 174. Information from the sensors 174 can also be used todetermine and implement operating parameters for the pump 710.

In some examples, the controller 714 is incorporated in a separate andremote electronic device in communication with the pump 710, such as adedicated electronic device, computer, tablet PC, or smart phone.Alternatively, the controller 714 can be included in the pump 710 and,for example, can control both a user interface for manually operatingthe pump 710, as well as system functions such as receiving andprocessing information from the sensors 174.

The controller 714 is configured to receive information from the one ormore sensors 174 and to store the information in the associatedcomputer-readable memory 716. For example, the controller 714 can beconfigured to receive information from the sensor 174 at a predeterminedrate, such as once every second, and to determine a conductance based onthe received information. In some examples, the algorithm forcalculating conductance can also include other sensor measurements, suchas urine temperature, to obtain a more robust determination ofconductance.

The controller 714 can also be configured to calculate patient physicalstatistics or diagnostic indicators that illustrate changes in thepatient's condition over time. For example, the system 700 can beconfigured to identify an amount of total sodium excreted. The totalsodium excreted may be based, for example, on a combination of flow rateand conductance over a period of time.

With continued reference to FIG. 13, the system 700 can further comprisea feedback device 720, such as a visual display or audio system, forproviding information to the user. In some examples, the feedback device720 can be integrally formed with the pump 710. Alternatively, thefeedback device 720 can be a separate dedicated or a multipurposeelectronic device, such as a computer, laptop computer, tablet PC, smartphone, or other handheld electronic devices. The feedback device 720 isconfigured to receive the calculated or determined measurements from thecontroller 714 and to present the received information to a user via thefeedback device 720. For example, the feedback device 720 may beconfigured to display current negative pressure (in mmHg) being appliedto the urinary tract. In other examples, the feedback device 720 isconfigured to display current flow rate of urine, temperature, currentconductance in mS/m of urine, total urine produced during the session,total sodium excreted during the session, other physical parameters, orany combination thereof.

In some examples, the feedback device 720 further comprises a userinterface module or component that allows the user to control operationof the pump 710. For example, the user can engage or turn off the pump710 via the user interface. The user can also adjust pressure applied bythe pump 710 to achieve a greater magnitude or rate of sodium excretionand fluid removal.

Optionally, the feedback device 720 and/or pump 710 further comprise adata transmitter 722 for sending information from the device 720 and/orpump 710 to other electronic devices or computer networks. The datatransmitter 722 can utilize a short-range or long-range datacommunications protocol. An example of a short-range data transmissionprotocol is Bluetooth®. Long-range data transmission networks include,for example, Wi-Fi or cellular networks. The data transmitter 722 cansend information to a patient's physician or caregiver to inform thephysician or caregiver about the patient's current condition.Alternatively, or in addition, information can be sent from the datatransmitter 722 to existing databases or information storage locations,such as, for example, to include the recorded information in a patient'selectronic health record (EHR).

With continued reference to FIG. 13, in addition to the urine sensors174, in some examples, the system 700 further comprises one or morepatient monitoring sensors 724. Patient monitoring sensors 724 caninclude invasive and non-invasive sensors for measuring informationabout the patient's urine composition, as discussed in detail above,blood composition (e.g., hematocrit ratio, analyte concentration,protein concentration, creatinine concentration) and/or blood flow(e.g., blood pressure, blood flow velocity). Hematocrit is a ratio ofthe volume of red blood cells to the total volume of blood. Normalhematocrit is about 25% to 40%, and preferably about 35% and 40% (e.g.,35% to 40% red blood cells by volume and 60% to 65% plasma).

Non-invasive patient monitoring sensors 724 can include pulse oximetrysensors, blood pressure sensors, heart rate sensors, and respirationsensors (e.g., a capnography sensor). Invasive patient monitoringsensors 724 can include invasive blood pressure sensors, glucosesensors, blood velocity sensors, hemoglobin sensors, hematocrit sensors,protein sensors, creatinine sensors, and others. In still otherexamples, sensors may be associated with an extracorporeal blood systemor circuit and configured to measure parameters of blood passing throughtubing of the extracorporeal system. For example, analyte sensors, suchas capacitance sensors or optical spectroscopy sensors, may beassociated with tubing of the extracorporeal blood system to measureparameter values of the patient's blood as it passes through the tubing.The patient monitoring sensors 724 can be in wired or wirelesscommunication with the pump 710 and/or controller 714.

In some examples, the controller 714 is configured to cause the pump 710to provide treatment for a patient based information obtained from theurine analyte sensor 174 and/or patient monitoring sensors 724, such asblood monitoring sensors. For example, pump 710 operating parameters canbe adjusted based on changes in the patient's blood hematocrit ratio,blood protein concertation, creatinine concentration, urine outputvolume, urine protein concentration (e.g., albumin), and otherparameters. For example, the controller 714 can be configured to receiveinformation about a blood hematocrit ratio or creatinine concentrationof the patient from the patient monitoring sensors 724 and/or analytesensors 174. The controller 714 can be configured to adjust operatingparameters of the pump 710 based on the blood and/or urine measurements.In other examples, hematocrit ratio may be measured from blood samplesperiodically obtained from the patient. Results of the tests can bemanually or automatically provided to the controller 714 for processingand analysis.

As discussed herein, measured hematocrit values for the patient can becompared to predetermined threshold or clinically acceptable values forthe general population. Generally, hematocrit levels for females arelower than for males. In other examples, measured hematocrit values canbe compared to patient baseline values obtained prior to a surgicalprocedure. When the measured hematocrit value is increased to within theacceptable range, the pump 710 may be turned off ceasing application ofnegative pressure to the ureter or kidneys. In a similar manner, theintensity of negative pressure can be adjusted based on measuredparameter values. For example, as the patient's measured parametersbegin to approach the acceptable range, intensity of negative pressurebeing applied to the ureter and kidneys can be reduced. In contrast, ifan undesirable trend (e.g., a decrease in hematocrit value, urine outputrate, and/or creatinine clearance) is identified, the intensity ofnegative pressure can be increased in order to produce a positivephysiological result. For example, the pump 710 may be configured tobegin by providing a low level of negative pressure (e.g., between about0.1 mmHg and 10 mmHg). The negative pressure may be incrementallyincreased until a positive trend in patient creatinine level isobserved. However, generally, negative pressure provided by the pump 710will not exceed about 50 mmHg.

With reference to FIGS. 14A and 14B, an exemplary pump 710 for use withthe system is illustrated. In some examples, the pump 710 is amicro-pump configured to draw fluid from the catheter(s) 1000 and havinga sensitivity or accuracy of about 10 mmHg or less. Desirably, the pump710 is capable of providing a range of flow of urine between 0.05 ml/minand 3 ml/min for extended periods of time, for example, for about 8hours to about 24 hours per day, for one (1) to about 30 days or longer.At 0.2 ml/min, it is anticipated that about 300 mL of urine per day iscollected by the system 700. The pump 710 can be configured to provide anegative pressure to the bladder of the patient, the negative pressureranging between about 0.1 mmHg and 50 mmHg or about 5 mmHg to about 20mmHg (gauge pressure at the pump 710). For example, a micro-pumpmanufactured by Langer Inc. (Model BT100-2J) can be used with thepresently disclosed system 700. Diaphragm aspirator pumps, as well asother types of commercially available pumps, can also be used for thispurpose. Peristaltic pumps can also be used with the system 700. Inother examples, a piston pump, vacuum bottle, or manual vacuum sourcecan be used for providing negative pressure. In other examples, thesystem can be connected to a wall suction source, as is available in ahospital, through a vacuum regulator for reducing negative pressure totherapeutically appropriate levels.

In some examples, at least a portion of the pump assembly can bepositioned within the patient's urinary tract, for example within thebladder. For example, the pump assembly can comprise a pump module and acontrol module coupled to the pump module, the control module beingconfigured to direct motion of the pump module. At least one (one ormore) of the pump module, the control module, or the power supply may bepositioned within the patient's urinary tract. The pump module cancomprise at least one pump element positioned within the fluid flowchannel to draw fluid through the channel. Some examples of suitablepump assemblies, systems and methods of use are disclosed in U.S. PatentApplication No. 62/550,259, entitled “Indwelling Pump for FacilitatingRemoval of Urine from the Urinary Tract”, filed concurrently herewith,which is incorporated by reference herein in its entirety.

In some examples, the pump 710 is configured for extended use and, thus,is capable of maintaining precise suction for extended periods of time,for example, for about 8 hours to about 24 hours per day, for 1 to about30 days or longer. Further, in some examples, the pump 710 is configuredto be manually operated and, in that case, includes a control panel 718that allows a user to set a desired suction value. The pump 710 can alsoinclude a controller or processor, which can be the same controller thatoperates the system 700 or can be a separate processor dedicated foroperation of the pump 710. In either case, the processor is configuredfor both receiving instructions for manual operation of the pump and forautomatically operating the pump 710 according to predeterminedoperating parameters. Alternatively, or in addition, operation of thepump 710 can be controlled by the processor based on feedback receivedfrom the plurality of sensors associated with the catheter.

In some examples, the processor is configured to cause the pump 710 tooperate intermittently. For example, the pump 710 may be configured toemit pulses of negative pressure followed by periods in which nonegative pressure is provided. In other examples, the pump 710 can beconfigured to alternate between providing negative pressure and positivepressure to produce an alternating flush and pump effect. For example, apositive pressure of about 0.1 mmHg to 20 mmHg, and preferably about 5mmHg to 20 mmHg can be provided followed by a negative pressure rangingfrom about 0.1 mmHg to 50 mmHg.

Treatment for Removing Excess Fluid from a Patient with Hemodilution

According to another aspect of the disclosure, a method for removingexcess fluid from a patient with hemodilution is provided. In someexamples, hemodilution can refer to an increase in a volume of plasma inrelation to red blood cells and/or a reduced concentration of red bloodcells in circulation, as may occur when a patient is provided with anexcessive amount of fluid. The method can involve measuring and/ormonitoring patient hematocrit levels to determine when hemodilution hasbeen adequately addressed. Low hematocrit levels are a commonpost-surgical or post-trauma condition that can lead to undesirabletherapeutic outcomes. As such, management of hemodilution and confirmingthat hematocrit levels return to normal ranges is a desirabletherapeutic result for surgical and post-surgical patient care.

Steps for removing excess fluid from a patient using the devices andsystems described herein are illustrated in FIG. 15. As shown in FIG.15, the treatment method comprises deploying a urinary tract catheter,such as the urine collection catheter configured to be deployed in thebladder or renal pelvis of the present invention, in the ureter and/orkidney of a patient such that flow of urine from the ureter and/orkidney, as shown at box 910. The catheter may be placed to avoidoccluding the ureter and/or kidney. In some examples, a fluid collectingportion of the catheter may be positioned in the renal pelvis of thepatient's kidney. In some examples, a ureter catheter may be positionedin each of the patient's kidneys. In other examples, a urine collectioncatheter may be deployed in the bladder or ureter. In some examples, theureteral catheter comprises one or more of any of the retention portionsdescribed herein. For example, the ureteral catheter can comprise a tubedefining a drainage lumen comprising a helical retention portion and aplurality of drainage ports. In other examples, the catheter can includean inflatable retention portion (e.g., a balloon catheter),funnel-shaped fluid collection and retention portion, or a pigtail coil.

As shown at box 912, the method further comprises applying negativepressure to the ureter and/or kidney through the catheter to induceproduction of urine in the kidney(s) and to extract urine from thepatient. Desirably, negative pressure is applied for a period of timesufficient to reduce the patient's blood creatinine levels by aclinically significant amount.

Negative pressure may continue to be applied for a predetermined periodof time. For example, a user may be instructed to operate the pump forthe duration of a surgical procedure or for a time period selected basedon physiological characteristics of the patient. In other examples,patient condition may be monitored to determine when sufficienttreatment has been provided. For example, as shown at box 914, themethod may further comprise monitoring the patient to determine when tocease applying negative pressure to the patient's ureter and/or kidneys.In a preferred and non-limiting example, a patient's hematocrit level ismeasured. For example, patient monitoring devices may be used toperiodically obtain hematocrit values. In other examples, blood samplesmay be drawn periodically to directly measure hematocrit. In someexamples, concentration and/or volume of urine expelled from the bodythrough the catheter may also be monitored to determine a rate at whichurine is being produced by the kidneys. In a similar manner, expelledurine output may be monitored to determine protein concentration and/orcreatinine clearance rate for the patient. Reduced creatinine andprotein concentration in urine may be indicative of over-dilution and/ordepressed renal function. Measured values can be compared to thepredetermined threshold values to assess whether negative pressuretherapy is improving patient condition, and should be modified ordiscontinued. For example, as discussed herein, a desirable range forpatient hematocrit may be between 25% and 40%. In other preferred andnon-limiting examples, as described herein, patient body weight may bemeasured and compared to a dry body weight. Changes in measured patientbody weight demonstrate that fluid is being removed from the body. Assuch, a return to dry body weight represents that hemodilution has beenappropriately managed and the patient is not over-diluted.

As shown at box 916, a user may cause the pump to cease providingnegative pressure therapy when a positive result is identified. In asimilar manner, patient blood parameters may be monitored to assesseffectiveness of the negative pressure being applied to the patient'skidneys. For example, a capacitance or analyte sensor may be placed influid communication with tubing of an extracorporeal blood managementsystem. The sensor may be used to measure information representative ofblood protein, oxygen, creatinine, and/or hematocrit levels. Measuredblood parameter values may be measured continuously or periodically andcompared to various threshold or clinically acceptable values. Negativepressure may continue to be applied to the patient's kidney or ureteruntil a measured parameter value falls within a clinically acceptablerange. Once a measured values fails within the threshold or clinicallyacceptable range, as shown at box 916, application of negative pressuremay cease.

Treatment of Patients Undergoing a Fluid Resuscitation Procedure

According to another aspect of the disclosure, a method for removingexcess fluid for a patient undergoing a fluid resuscitation procedure,such as coronary graft bypass surgery, by removing excess fluid from thepatient is provided. During fluid resuscitation, solutions such assaline solutions and/or starch solutions, are introduced to thepatient's bloodstream by a suitable fluid delivery process, such as anintravenous drip. For example, in some surgical procedures, a patientmay be supplied with between 5 and 10 times a normal daily intake offluid. Fluid replacement or fluid resuscitation can be provided toreplace bodily fluids lost through sweating, bleeding, dehydration, andsimilar processes. In the case of a surgical procedure such as coronarygraft bypass, fluid resuscitation is provided to help maintain apatient's fluid balance and blood pressure within an appropriate rate.Acute kidney injury (AKI) is a known complication of coronary arterygraft bypass surgery. AKI is associated with a prolonged hospital stayand increased morbidity and mortality, even for patients who do notprogress to renal failure. See Kim, et al., Relationship between aperioperative intravenous fluid administration strategy and acute kidneyinjury following off-pump coronary artery bypass surgery: anobservational study, Critical Care 19:350 (1995). Introducing fluid toblood also reduces hematocrit levels which has been shown to furtherincrease mortality and morbidity. Research has also demonstrated thatintroducing saline solution to a patient may depress renal functionaland/or inhibit natural fluid management processes. As such, appropriatemonitoring and control of renal function may produce improved outcomesand, in particular, may reduce post-operative instances of AKI.

A method of treating a patient undergoing fluid resuscitation isillustrated in FIG. 16. As shown at box 3010, the method comprisesdeploying a ureteral catheter in the ureter and/or kidney of a patientsuch that flow of urine from the ureter and/or kidney is not preventedby occlusion of the ureter and/or kidney. For example, a fluidcollecting portion of the catheter may be positioned in the renalpelvis. In other examples, the catheter may be deployed in the bladderor ureter. The catheter can comprise one or more of the urine collectioncatheters configured to be deployed in the bladder or renal pelvis asdescribed herein. For example, the catheter can comprise a tube defininga drainage lumen and comprising a helical retention portion and aplurality of drainage ports. In other examples, the catheter can includean inflatable retention portion (e.g., a balloon catheter) or a pigtailcoil.

As shown at box 3012, optionally, a bladder catheter may also bedeployed in the patient's bladder. For example, the bladder catheter maybe positioned to seal the urethra opening to prevent passage of urinefrom the body through the urethra. The bladder catheter can include aninflatable anchor (e.g., a Foley catheter) for maintaining the distalend of the catheter in the bladder. As described herein, otherarrangements of coils and helices may also be used to obtain properpositioning of the bladder catheter. The bladder catheter can beconfigured to collect urine which entered the patient's bladder prior toplacement of the ureteral catheter(s). The bladder catheter may alsocollect urine which flows past the fluid collection portion(s) of theureteral catheter and enters the bladder. In some examples, a proximalportion of the ureteral catheter may be positioned in a drainage lumenof the bladder catheter. In a similar manner, the bladder catheter maybe advanced into the bladder using the same guidewire used forpositioning of the ureteral catheter(s). In some examples, negativepressure may be provided to the bladder through the drainage lumen ofthe bladder catheter. In other examples, negative pressure may only beapplied to the ureteral catheter(s). In that case, the bladder catheterdrains by gravity.

As shown at box 3014, following deployment of the ureteral catheter(s),negative pressure is applied to the ureter and/or kidney through theureteral catheter(s). For example, negative pressure can be applied fora period of time sufficient to extract urine comprising a portion of thefluid provided to the patient during the fluid resuscitation procedure.As described herein, negative pressure can be provided by an externalpump connected to a proximal end or port of the catheter. The pump canbe operated continually or periodically dependent on therapeuticrequirements of the patient. In some cases, the pump may alternatebetween applying negative pressure and positive pressure.

Negative pressure may continue to be applied for a predetermined periodof time. For example, a user may be instructed to operate the pump forthe duration of a surgical procedure or for a time period selected basedon physiological characteristics of the patient. In other examples,patient condition may be monitored to determine when a sufficient amountof fluid has been drawn from the patient. For example, as shown at box3016, fluid expelled from the body may be collected and a total volumeof obtained fluid may be monitored. In that case, the pump can continueto operate until a predetermined fluid volume has been collected fromthe ureteral and/or bladder catheters. The predetermined fluid volumemay be based, for example, on a volume of fluid provided to the patientprior to and during the surgical procedure. As shown at box 3018,application of negative pressure to the ureter and/or kidneys is stoppedwhen the collected total volume of fluid exceeds the predetermined fluidvolume.

In other examples, operation of the pump can be determined based onmeasured physiological parameters of the patient, such as measuredcreatinine clearance, blood creatinine level, or hematocrit ratio. Forexample, as shown at box 3020, urine collected form the patient may beanalyzed by one or more sensors associated with the catheter and/orpump. The sensor can be a capacitance sensor, analyte sensor, opticalsensor, or similar device configured to measure urine analyteconcentration. In a similar manner, as shown at box 3022, a patient'sblood creatinine or hematocrit level could be analyzed based oninformation obtain from the patient monitoring sensors discussedhereinabove. For example, a capacitance sensor may be placed in anexisting extracorporeal blood system. Information obtained by thecapacitance sensor may be analyzed to determine a patient's hematocritratio. The measured hematocrit ratio may be compared to certain expectedor therapeutically acceptable values. The pump may continue to applynegative pressure to the patient's ureter and/or kidney until measuredvalues within the therapeutically acceptable range are obtained. Once atherapeutically acceptable value is obtained, application of negativepressure may be stopped as shown at box 3018.

In other examples, patient body weight may be measured to assess whetherfluid is being removed from the patient by the applied negative pressuretherapy. For example, a patient's measured bodyweight (including fluidintroduced during a fluid resuscitation procedure) can be compared to apatient's dry body weight. As used herein, dry weights is defined asnormal body weight measured when a patient is not over-diluted. Forexample, a patient who is not experiencing one or more of: elevatedblood pressure, lightheadedness or cramping, swelling of legs, feet,arms, hands, or around the eyes, and who is breathing comfortably,likely does not have excess fluid. A weight measured when the patient isnot experiencing such symptoms can be a dry body weight. Patient weightcan be measured periodically until the measured weight approaches thedry body weight. When the measured weight approaches (e.g., is withinbetween 5% and 10% of dry body weight), as shown at box 3018,application of negative pressure can be stopped.

EXPERIMENTAL EXAMPLES

Inducement of negative pressure within the renal pelvis of farm swinewas performed for the purpose of evaluating effects of negative pressuretherapy on renal congestion in the kidney. An objective of these studieswas to demonstrate whether a negative pressure delivered into the renalpelvis significantly increases urine output in a swine model of renalcongestion. In Example 1, a pediatric Fogarty catheter, normally used inembolectomy or bronchoscopy applications, was used in the swine modelsolely for proof of principle for inducement of negative pressure in therenal pelvis. It is not suggested that a Fogarty catheter be used inhumans in clinical settings to avoid injury of urinary tract tissues.

Example 1

Method

Four farm swine 800 were used for purposes of evaluating effects ofnegative pressure therapy on renal congestion in the kidney. As shown inFIG. 17, pediatric Fogarty catheters 812, 814 were inserted to the renalpelvis region 820, 821 of each kidney 802, 804 of the four swine 800.The catheters 812, 814 were deployed within the renal pelvis region byinflating an expandable balloon to a size sufficient to seal the renalpelvis and to maintain the position of the balloon within the renalpelvis. The catheters 812, 814 extend from the renal pelvis 802, 804,through a bladder 810 and urethra 816, and to fluid collectioncontainers external to the swine.

Urine output of two animals was collected for a 15 minute period toestablish a baseline for urine output volume and rate. Urine output ofthe right kidney 802 and the left kidney 804 were measured individuallyand found to vary considerably. Creatinine clearance values were alsodetermined.

Renal congestion (e.g., congestion or reduced blood flow in the veins ofthe kidney) was induced in the right kidney 802 and the left kidney 804of the animal 800 by partially occluding the inferior vena cava (IVC)with an inflatable balloon catheter 850 just above to the renal veinoutflow. Pressure sensors were used to measure IVC pressure. Normal IVCpressures were 1-4 mmHg. By inflating the balloon of the catheter 850 toapproximately three quarters of the IVC diameter, the IVC pressures wereelevated to between 15-25 mmHg. Inflation of the balloon toapproximately three quarters of IVC diameter resulted in a 50-85%reduction in urine output. Full occlusion generated IVC pressures above28 mmHg and was associated with at least a 95% reduction in urineoutput.

One kidney of each animal 800 was not treated and served as a control(“the control kidney 802”). The ureteral catheter 812 extending from thecontrol kidney was connected to a fluid collection container 819 fordetermining fluid levels. One kidney (“the treated kidney 804”) of eachanimal was treated with negative pressure from a negative pressuresource (e.g., a therapy pump 818 in combination with a regulatordesigned to more accurately control the low magnitude of negativepressures) connected to the ureteral catheter 814. The pump 818 was anAir Cadet Vacuum Pump from Cole-Parmer Instrument Company (Model No.EW-07530-85). The pump 818 was connected in series to the regulator. Theregulator was an V-800 Series Miniature Precision Vacuum Regulator—1/8NPT Ports (Model No. V-800-10-W/K), manufactured by Airtrol ComponentsInc.

The pump 818 was actuated to induce negative pressure within the renalpelvis 820, 821 of the treated kidney according to the followingprotocol. First, the effect of negative pressure was investigated in thenormal state (e.g., without inflating the IVC balloon). Four differentpressure levels (−2, −10, −15, and −20 mmHg) were applied for 15 minuteseach and the rate of urine produced and creatinine clearance weredetermined. Pressure levels were controlled and determined at theregulator. Following the −20 mmHg therapy, the IVC balloon was inflatedto increase the pressure by 15-20 mmHg. The same four negative pressurelevels were applied. Urine output rate and creatinine clearance rate forthe congested control kidney 802 and treated kidney 804 were obtained.The animals 800 were subject to congestion by partial occlusion of theIVC for 90 minutes. Treatment was provided for 60 minutes of the 90minute congestion period.

Following collection of urine output and creatinine clearance data,kidneys from one animal were subjected to gross examination then fixedin a 10% neutral buffered formalin. Following gross examination,histological sections were obtained, examined, and magnified images ofthe sections were captured. The sections were examined using an uprightOlympus BX41 light microscope and images were captured using an OlympusDP25 digital camera. Specifically, photomicrograph images of the sampledtissues were obtained at low magnification (20× original magnification)and high magnification (100× original magnification). The obtainedimages were subjected to histological evaluation. The purpose of theevaluation was to examine the tissue histologically and to qualitativelycharacterize congestion and tubular degeneration for the obtainedsamples.

Surface mapping analysis was also performed on obtained slides of thekidney tissue. Specifically, the samples were stained and analyzed toevaluate differences in size of tubules for treated and untreatedkidneys. Image processing techniques calculated a number and/or relativepercentage of pixels with different coloration in the stained images.Calculated measurement data was used to determine volumes of differentanatomical structures.

Results

Urine Output and Creatinine Clearance

Urine output rates were highly variable. Three sources of variation inurine output rate were observed during the study. The inter-individualand hemodynamic variability were anticipated sources of variabilityknown in the art. A third source of variation in urine output, uponinformation and belief believed to be previously unknown, was identifiedin the experiments discussed herein, namely, contralateralintra-individual variability in urine output.

Baseline urine output rates were 0.79 ml/min for one kidney and 1.07ml/min for the other kidney (e.g., a 26% difference). The urine outputrate is a mean rate calculated from urine output rates for each animal.

When congestion was provided by inflating the IVC balloon, the treatedkidney urine output dropped from 0.79 ml/min to 0.12 ml/min (15.2% ofbaseline). In comparison, the control kidney urine output rate duringcongestion dropped from 1.07 ml/min to 0.09 ml/min (8.4% of baseline).Based on urine output rates, a relative increase in treated kidney urineoutput compared to control kidney urine output was calculated, accordingto the following equation:(Therapy Treated/Baseline Treated)/(Therapy Control/BaselineControl)=Relative increase(0.12 ml/min/0.79 ml/min)/(0.09 ml/min/1.07ml/min)=180.6%

Thus, the relative increase in treated kidney urine output rate was180.6% compared to control. This result shows a greater magnitude ofdecrease in urine production caused by congestion on the control sidewhen compared to the treatment side. Presenting results as a relativepercentage difference in urine output adjusts for differences in urineoutput between kidneys.

Creatinine clearance measurements for baseline, congested, and treatedportions for one of the animals are shown in FIG. 18.

Gross Examination and Histological Evaluation

Based on gross examination of the control kidney (right kidney) andtreated kidney (left kidney), it was determined that the control kidneyhad a uniformly dark red-brown color, which corresponds with morecongestion in the control kidney compared to the treated kidney.Qualitative evaluation of the magnified section images also notedincreased congestion in the control kidney compared to the treatedkidney. Specifically, as shown in Table 1, the treated kidney exhibitedlower levels of congestion and tubular degeneration compared to thecontrol kidney. The following qualitative scale was used for evaluationof the obtained slides.

TABLE 1 Lesion Score Congestion None: 0 Mild: 1 Moderate: 2 Marked: 3Severe: 4 Tubular degeneration None: 0 Mild: 1 Moderate: 2 Marked: 3Severe: 4 TABULATED RESULTS Histologic lesions Tubular Animal ID/Organ/Slide hyaline Gross lesion number Congestion casts Granulomas 6343/LeftKidney/ R16-513-1 1 1 0 Normal 6343/Left Kidney/ R16-513-2 1 1 0 Normalwith hemorrhagic streak 6343/Right Kidney/ R16-513-3 2 2 1 Congestion6343/Right Kidney/ R16-513-4 2 1 1 Congestion

As shown in Table 1, the treated kidney (left kidney) exhibited onlymild congestion and tubular degeneration. In contrast, the controlkidney (right kidney) exhibited moderate congestion and tubulardegeneration. These results were obtained by analysis of the slidesdiscussed below.

FIGS. 19A and 19B are low and high magnification photomicrographs of theleft kidney (treated with negative pressure) of the animal. Based on thehistological review, mild congestion in the blood vessels at thecorticomedullary junction was identified, as indicated by the arrows. Asshown in FIG. 19B, a single tubule with a hyaline cast (as identified bythe asterisk) was identified.

FIGS. 19C and 19D are low and high resolution photomicrographs of thecontrol kidney (right kidney). Based on the histological review,moderate congestion in the blood vessel at the corticomedullary junctionwas identified, as shown by the arrows in FIG. 19C. As shown in FIG.19D, several tubules with hyaline casts were present in the tissuesample (as identified by asterisks in the image). Presence of asubstantial number of hyaline casts is evidence of hypoxia.

Surface mapping analysis provided the following results. The treatedkidney was determined to have 1.5 times greater fluid volume in Bowman'sspace and 2 times greater fluid volume in tubule lumen. Increased fluidvolume in Bowman's space and the tubule lumen corresponds to increasedurine output. In addition, the treated kidney was determined to have 5times less blood volume in capillaries compared to the control kidney.The increased volume in the treated kidney appears to be a result of (1)a decrease in individual capillary size compared to the control and (2)an increase in the number of capillaries without visible red blood cellsin the treated kidney compared to the control kidney, an indicator ofless congestion in the treated organ.

Summary

These results indicate that the control kidney had more congestion andmore tubules with intraluminal hyaline casts, which representprotein-rich intraluminal material, compared to the treated kidney.Accordingly, the treated kidney exhibits a lower degree of loss of renalfunction. While not intending to be bound by theory, it is believed thatas severe congestion develops in the kidney, hypoxemia of the organfollows. Hypoxemia interferes with oxidative phosphorylation within theorgan (e.g., ATP production). Loss of ATP and/or a decrease in ATPproduction inhibits the active transport of proteins causingintraluminal protein content to increase, which manifests as hyalinecasts. The number of renal tubules with intraluminal hyaline castscorrelates with the degree of loss of renal function. Accordingly, thereduced number of tubules in the treated left kidney is believed to bephysiologically significant. While not intending to be bound by theory,it is believed that these results show that damage to the kidney can beprevented or inhibited by applying negative pressure to a catheterinserted into the renal pelvis to facilitate urine output.

Example 2

Method

Inducement of negative pressure within the renal pelvis of farm swinewas performed for the purpose of evaluating effects of negative pressuretherapy on hemodilution of the blood. An objective of these studies wasto demonstrate whether a negative pressure delivered into the renalpelvis significantly increases urine output in a swine model of fluidresuscitation.

Two pigs were sedated and anesthetized using ketamine, midazolam,isoflurane and propofol. One animal (#6543) was treated with a ureteralcatheter and negative pressure therapy as described herein. The other,which received a Foley type bladder catheter, served as a control(#6566). Following placement of the catheters, the animals weretransferred to a sling and monitored for 24 hours.

Fluid overload was induced in both animals with a constant infusion ofsaline (125 mL/hour) during the 24 hour follow-up. Urine output volumewas measured at 15 minute increments for 24 hours. Blood and urinesamples were collected at 4 hour increments. As shown in FIG. 17, atherapy pump 818 was set to induce negative pressure within the renalpelvis 820, 821 (shown in FIG. 17) of both kidneys using a pressure of−45 mmHg (+/−2 mmHg).

Results

Both animals received 7 L of saline over the 24 hour period. The treatedanimal produced 4.22 L of urine while the control produced 2.11 L. Atthe end of 24 hours, the control had retained 4.94 L of the 7 Ladministered, while the treated animal retained 2.81 L of the 7 Ladministered. FIG. 20 illustrates the change in serum albumin. Thetreated animal had a 6% drop in the serum albumin concentration over 24hours, while the control animal had a 29% drop.

Summary

While not intending to be bound by theory, it is believed that thecollected data supports the hypothesis that fluid overload inducesclinically significant impact on renal function and, consequentlyinduces hemodilution. In particular, it was observed that administrationof large quantities of intravenous saline cannot be effectively removedby even healthy kidneys. The resulting fluid accumulation leads tohemodilution. The data also appears to support the hypothesis thatapplying negative pressure diuresis therapy to fluid overloaded animalscan increase urine output, improve net fluid balance and decrease theimpact of fluid resuscitation on development of hemodilution.

The preceding examples and embodiments of the invention have beendescribed with reference to various examples. Modifications andalterations will occur to others upon reading and understanding theforegoing examples. Accordingly, the foregoing examples are not to beconstrued as limiting the disclosure.

What is claimed is:
 1. A ureteral catheter configured to be deployed ina urinary tract of a patient, comprising: an elongated tube comprising aproximal portion configured for placement in a ureter of the patient, adistal portion comprising a distal end, and a sidewall extending betweena proximal end and the distal end of the elongated tube defining atleast one drainage lumen extending through the tube, the sidewallcomprising a drainage portion which allows fluid to pass through thesidewall and into the drainage lumen; and a permeable tissue supportdirectly or indirectly connected to the distal portion of the elongatedtube and extending axially and/or radially therefrom, the tissue supportbeing configured to be deployed in the urinary tract to maintain thedistal end of the elongated tube at a predetermined position in aureter, a renal pelvis, or a kidney of the patient, wherein, whendeployed, the permeable tissue support defines a three-dimensional shapeof sufficient size to permit flow of at least a portion of fluid fromthe urinary tract through the tissue support and drainage portion of theelongated tube to the at least one drainage lumen upon application ofnegative pressure through the catheter, and wherein a diameter of thethree-dimensional shape at a distal end of the permeable tissue supportis greater than a diameter of the three dimensional shape at a proximalend of the permeable tissue support at the distal end of the elongatedtube.
 2. The catheter of claim 1, wherein, when deployed, the permeabletissue support at least partially encloses the drainage portion of thesidewall.
 3. The catheter of claim 1, wherein the permeable tissuesupport comprises a permeable material.
 4. The catheter of claim 3,wherein the permeable material comprises at least one of biocompatiblepolymer fiber(s); metallic fiber(s), porous film(s), film(s) comprisingone or more apertures, fabric(s), or any combination thereof.
 5. Thecatheter of claim 3, wherein the permeable material has a thickness offrom about 0.5 mm to about 5 mm.
 6. The catheter of claim 1, wherein thepermeable tissue support comprises a plurality of elongated membershaving a first end and/or a second end connected to the elongated tubewoven together to form a mesh of elongated members.
 7. The catheter ofclaim 1, wherein, when deployed in the patient's ureter, renal pelvis,or kidney, the permeable tissue support is configured to maintain avolume of the three dimensional shape when an interior of the ureter, arenal pelvis, or kidney is exposed to negative pressure.
 8. The catheterof claim 1, wherein, when deployed in the patient's ureter, renalpelvis, or kidney, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of theureter, renal pelvis, or kidney is exposed to negative pressure of from5 to 150 mmHg.
 9. The catheter of claim 1, wherein, when deployed in thepatient's ureter, renal pelvis, or kidney, the permeable tissue supportis configured to inhibit mucosal tissue from occluding at least aportion of the drainage portion of the sidewall.
 10. The catheter ofclaim 1, wherein the permeable tissue support has a maximum outerdiameter of from about 10 mm to about 100 mm.
 11. The catheter of claim1, wherein a length between a proximal end and a distal end of thepermeable tissue support is from about 10 mm to about 100 mm.
 12. Thecatheter of claim 1, wherein the elongated tube has an outer diameter offrom about 0.5 mm to about 10 mm.
 13. The catheter of claim 1, whereinthe elongated tube has an inner diameter of from about 0.5 mm to about 9mm.
 14. The catheter of claim 1, wherein, when deployed, the threedimensional shape has a volume of from 0.1 cm³ to 500 cm³.
 15. Thecatheter of claim 1, wherein, when deployed, a middle portion of thepermeable tissue support bulges radially outward from proximal anddistal ends of the permeable tissue support, such that an outer diameterof the permeable tissue support increases from the proximal end to themiddle portion thereof and decreases from the middle portion to thedistal end thereof.
 16. The catheter of claim 1, wherein, when deployed,the permeable tissue support comprises at least one middle portionlocated between a proximal portion and a distal portion of the tissuesupport, and wherein the middle portion has a minimum outer diameterwhich is less than a maximum outer diameter of the proximal portion andthe distal portion of the permeable tissue support.
 17. The catheter ofclaim 16, wherein the minimum outer diameter of the middle portion isfrom about 2.5 mm to about 20 mm less than the maximum outer diameter ofthe proximal portion or the distal portion of the tissue support. 18.The catheter of claim 16, wherein the minimum outer diameter of themiddle portion is from about equal to an outer diameter of the elongatedtube to about 40 mm greater than the outer diameter of the elongatedtube.
 19. The catheter of claim 16, wherein the minimum outer diameterof the middle portion is from about 10% to about 99% less than themaximum outer diameter of the proximal portion or the distal portion ofthe tissue support.
 20. The catheter of claim 1, wherein the drainageportion of the sidewall comprises a perforated section of tubingcomprising at least one perforation permitting fluid to flow through thesidewall of the elongated tube into the at least one drainage lumen. 21.The catheter of claim 20, wherein the at least one perforation has oneor more shapes, each shape being selected from at least one of acircular shape, an elliptical shape, a square shape, a regular polygonalshape, an irregular circular shape, or an irregular polygonal shape, orcombinations thereof.
 22. The catheter of claim 20, wherein the at leastone perforation has a diameter of about 0.05 mm to about 2.0 mm.
 23. Thecatheter of claim 20, wherein, when deployed in the patient's ureter,renal pelvis, or kidney, the permeable tissue support is configured toinhibit any portion of a wall of the ureter, renal pelvis, or kidneyfrom occluding the at least one perforation of the drainage portion upondelivery of negative pressure to an interior of the ureter, renalpelvis, or kidney through the drainage lumen of the elongated tube. 24.The catheter of claim 1, wherein, when deployed in the patient's ureter,renal pelvis, or kidney, the permeable tissue support is configured toinhibit any portion of the ureter, renal pelvis, or kidney wall fromoccluding or obstructing ureteral orifice upon delivery of negativepressure to the ureter, renal pelvis, or kidney through the drainagelumen of the tube.
 25. The catheter of claim 1, further comprising atleast one collar slidably connected to the elongated tube, wherein atleast a portion of the permeable tissue support is connected to thecollar.
 26. The catheter of claim 25, wherein sliding the collar alongthe elongated tube deploys or retracts the permeable tissue support. 27.The catheter of claim 1, wherein the elongated tube comprises an innertube, further comprising an elongated outer tube at least partiallysurrounding the inner tube, the outer tube having a proximal endportion, a distal end portion, and a sidewall extending therebetween,wherein a distal portion of the permeable tissue support is connected tothe inner tube and a proximal portion of the permeable tissue support isconnected to the outer elongated tube.
 28. The catheter of claim 27,wherein sliding the inner elongated tube relative to the outer elongatedtube causes at least one of deployment and retraction of the permeabletissue support.
 29. The catheter of claim 27, wherein the drainageportion of the sidewall comprises one or more perforations, and whereinat least one perforation is at least partially enclosed by the permeabletissue support, when the permeable tissue support is deployed.
 30. Thecatheter of claim 1, further comprising a delivery catheter comprising aproximal end configured to remain external to the body, a distal end forinsertion into the ureter, renal pelvis, or kidney, a sidewall extendingtherebetween, and at least one lumen sized to receive the elongated tubeand permeable tissue support, wherein the delivery catheter isconfigured to maintain the permeable tissue support in a retractedposition during insertion of the permeable tissue support to the urinarytract of the patient.
 31. The catheter of claim 30, wherein the deliverycatheter has an inner diameter of from about 5 mm to about 20 mm. 32.The catheter of claim 30, wherein the permeable tissue support is biasedto a deployed position, such that when pushed from the distal end of thedelivery catheter, the permeable tissue support adopts its deployedconfiguration.
 33. The catheter of claim 1, wherein the permeable tissuesupport is configured to transition from a retracted position in whichat least a portion of an inner surface of the tissue support contacts anouter surface of the sidewall to a deployed position in which theportion of the inner surface of the tissue support is spaced apart fromthe sidewall.
 34. The ureteral catheter of claim 1, wherein the tissuesupport comprises a substantially cylindrical distal portion and taperedproximal portion.
 35. The ureteral catheter of claim 1, wherein thetissue support comprises a substantially flat distal surface.
 36. Theureteral catheter of claim 1, wherein, when deployed, thethree-dimensional shape is positioned to maintain patency of fluid flowbetween the kidney and the proximal end of the tube such that at least aportion of the fluid flow flows through the tissue support uponapplication of negative pressure through the catheter.
 37. The ureteralcatheter of claim 1, wherein, when deployed, the tissue support isconfigured to inhibit ureteral, renal pelvis or kidney tissue fromoccluding at least a portion of the expandable retention portion ordistal end of the tube upon application of negative pressure through thecatheter.
 38. A method of inducing a negative pressure to a urinarytract of a patient for enhancing urine excretion therefrom, the methodcomprising: inserting a distal portion of an elongated tube of aureteral catheter into the urinary tract, the elongated tube comprisinga proximal portion configured for placement in a ureter of the patient,a distal portion comprising a distal end, and a sidewall extendingbetween a proximal end and the distal end of the elongated tube definingat least one drainage lumen extending through the tube, the sidewallcomprising a drainage portion which allows fluid to pass through thesidewall and into the drainage lumen; deploying a permeable tissuesupport directly or indirectly connected to and extending axially and/orradially from the elongated tube at a predetermined position in aureter, a renal pelvis, or a kidney of the patient, wherein thepermeable tissue support is configured to be deployed in the urinarytract to maintain the distal end of the elongated tube at thepredetermined position, and wherein, when deployed, the permeable tissuesupport defines a three-dimensional shape of sufficient size to permitflow of at least a portion of fluid from the urinary tract through thepermeable tissue support and drainage portion of the sidewall to the atleast one drainage lumen extending through the elongated tube uponapplication of negative pressure through the catheter, and wherein adiameter of the three-dimensional shape at a distal end of the permeabletissue support is greater than a diameter of the three dimensional shapeat a proximal end of the permeable tissue support at the distal end ofthe elongated tube; and inducing a negative pressure through the atleast one drainage lumen of the elongated tube to draw urine from theurinary tract into the drainage lumen.
 39. The method of claim 38,wherein, when deployed, the permeable tissue support at least partiallyencloses the drainage portion of the sidewall.
 40. The method of claim38, wherein the permeable tissue support comprises a permeable material.41. The method of claim 40, wherein the permeable material comprises atleast one of biocompatible polymer fiber(s); metallic fiber(s), porousfilm(s), film(s) comprising one or more apertures, fabric(s), or anycombination thereof.
 42. The method of claim 38, wherein, when deployedin the patient's ureter, renal pelvis, or kidney, the permeable tissuesupport is configured to maintain a volume of the three dimensionalshape when an interior of the ureter, renal pelvis, or kidney is exposedto negative pressure.
 43. The method of claim 38, wherein, when deployedin the patient's ureter, renal pelvis, or kidney, the permeable tissuesupport is configured to maintain a volume of the three dimensionalshape when an interior of the ureter, renal pelvis, or kidney is exposedto negative pressure of from about 5 mmHg to about 150 mmHg.
 44. Themethod of claim 38, wherein inducing the negative pressure in thedrainage lumen comprises coupling a mechanical pump in fluidcommunication with the proximal end of the drainage lumen to draw urinefrom the urinary tract into the drainage lumen through the drainageportion of the sidewall.
 45. The method of claim 38, wherein inducingnegative pressure comprises applying a negative pressure of from about0.1 mmHg to about 150 mmHg to the proximal end of the elongated tube.46. The method of claim 38, wherein the elongated tube is inserted intothe ureter in a delivery catheter, and wherein deploying the permeabletissue support comprises retracting the delivery catheter to expose thepermeable tissue support.
 47. The method of claim 46, wherein thepermeable tissue support adopts a deployed position when the deliverycatheter is retracted.
 48. The method of claim 38, wherein the tissuesupport comprises a substantially cylindrical distal portion.
 49. Themethod of claim 38, wherein the tissue support comprises a substantiallycylindrical distal portion and tapered proximal portion.
 50. The methodof claim 38, wherein the tissue support comprises a substantially flatdistal surface.
 51. The method of claim 38, wherein, when deployed, thethree-dimensional shape is positioned to maintain patency of fluid flowbetween the kidney and the proximal end of the tube such that at least aportion of the fluid flow flows through the tissue support uponapplication of negative pressure through the catheter.
 52. The method ofclaim 38, wherein, when deployed, the tissue support is configured toinhibit ureteral, renal pelvis or kidney tissue from occluding at leasta portion of the expandable retention portion or distal end of the tubeupon application of negative pressure through the catheter.
 53. A systemfor drawing urine from a urinary tract of a patient, the systemcomprising: a ureteral catheter comprising: an elongated tube comprisinga proximal portion configured for placement in a ureter of the patient,a distal portion comprising a distal end, and a sidewall extendingbetween a proximal end and the distal end of the elongated tube definingat least one drainage lumen extending through the tube, the sidewallcomprising a drainage portion which allows fluid to pass through thesidewall and into the drainage lumen; and a permeable tissue supportdirectly or indirectly connected to the distal portion of the elongatedtube and extending axially and/or radially therefrom, the tissue supportbeing configured to be deployed in the urinary tract to maintain thedistal end of the elongated tube at a predetermined position in aureter, a renal pelvis, or a kidney of the patient, wherein, whendeployed, the permeable tissue support defines a three-dimensional shapeof sufficient size to permit flow of at least a portion of fluid fromthe urinary tract through the permeable tissue support and drainageportion of the sidewall to the at least one drainage lumen extendingthrough the elongated tube upon application of negative pressure throughthe catheter, and wherein a diameter of the three-dimensional shape at adistal end of the permeable tissue support is greater than a diameter ofthe three dimensional shape at a proximal end of the permeable tissuesupport at the distal end of the elongated tube; and a pump in fluidconnection with the drainage lumen of the elongated tube, wherein thepump is configured to introduce negative pressure through the drainagelumen to the urinary tract of the patient to draw urine from the urinarytract.
 54. The system of claim 53, wherein the permeable tissue supportat least partially encloses the open distal end of the elongated tube.55. The system of claim 53, wherein the permeable tissue supportcomprises a permeable material comprising at least one of biocompatiblepolymer fiber(s); metallic fiber(s), porous film(s), film(s) comprisingone or more apertures, fabric(s), or any combination thereof.
 56. Thesystem of claim 53, wherein, when deployed in the patient's ureter,renal pelvis, or kidney, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of theureter, renal pelvis, or kidney is exposed to negative pressure.
 57. Thesystem of claim 53, wherein, when deployed in the patient's ureter,renal pelvis, or kidney, the permeable tissue support is configured tomaintain a volume of the three dimensional shape when an interior of theureter, renal pelvis, or kidney is exposed to negative pressure of fromabout 5 mmHg to about 150 mmHg.
 58. The system of claim 53, wherein,when deployed in the patient's ureter, renal pelvis, or kidney, thepermeable tissue support is configured to inhibit mucosal tissue fromoccluding at least a portion of the drainage portion of the sidewall.59. The system of claim 53, wherein the pump provides an accuracy ofabout 10 mmHg or less.
 60. The system of claim 53, wherein the pump isconfigured to provide a negative pressure of from about 0.1 mmHg toabout 150 mmHg.
 61. The system of claim 53, wherein the pump isconfigured to provide intermittent negative pressure.
 62. The system ofclaim 53, wherein the pump is configured to alternate between providingnegative pressure and providing positive pressure.
 63. The system ofclaim 53, wherein the pump is configured to alternate between providingnegative pressure and equalizing pressure to atmosphere.
 64. Theureteral catheter of claim 1, wherein the tissue support comprises asubstantially cylindrical distal portion.
 65. The system of claim 53,wherein the tissue support comprises a substantially cylindrical distalportion.
 66. The system of claim 53, wherein the tissue supportcomprises a substantially cylindrical distal portion and taperedproximal portion.
 67. The system of claim 53, wherein the tissue supportcomprises a substantially flat distal surface.
 68. The system of claim53, wherein, when deployed, the three-dimensional shape is positioned tomaintain patency of fluid flow between the kidney and the proximal endof the tube such that at least a portion of the fluid flow flows throughthe tissue support upon application of negative pressure through thecatheter.
 69. The system of claim 53, wherein, when deployed, the tissuesupport is configured to inhibit ureteral, renal pelvis or kidney tissuefrom occluding at least a portion of the expandable retention portion ordistal end of the tube upon application of negative pressure through thecatheter.